PittsburghV1, Main, Exploration, bibRecord, 002C67

GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy

Identifieur interne : 002C67 ( Main/Exploration ); précédent : 002C66; suivant : 002C68

GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy

Auteurs : Linda Broer [Pays-Bas] ; Aron S. Buchman ; Joris Deelen [Pays-Bas] ; Daniel S. Evans ; Jessica D. Faul ; Kathryn L. Lunetta ; Paola Sebastiani ; Jennifer A. Smith ; Albert V. Smith [Islande] ; Toshiko Tanaka ; Lei Yu ; Alice M. Arnold ; Thor Aspelund [Islande] ; Emelia J. Benjamin ; Philip L. De Jager ; Gudny Eirkisdottir [Islande] ; Denis A. Evans ; Melissa E. Garcia ; Albert Hofman [Pays-Bas] ; Robert C. Kaplan ; Sharon L. R. Kardia ; Douglas P. Kiel ; Ben A. Oostra [Pays-Bas] ; Eric S. Orwoll ; Neeta Parimi ; Bruce M. Psaty ; Fernando Rivadeneira [Pays-Bas] ; Jerome I. Rotter ; Sudha Seshadri ; Andrew Singleton ; Henning Tiemeier [Pays-Bas] ; André G. Uitterlinden [Pays-Bas] ; Wei Zhao ; Stefania Bandinelli [Italie] ; David A. Bennett ; Luigi Ferrucci ; Vilmundur Gudnason [Islande] ; Tamara B. Harris ; David Karasik [Israël] ; Lenore J. Launer ; Thomas T. Perls ; P. Eline Slagboom [Pays-Bas] ; Gregory J. Tranah ; David R. Weir ; Anne B. Newman ; Cornelia M. Van Duijn [Pays-Bas] ; Joanne M. Murabito

Source :

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences [ 1079-5006 ] ; 2014.

RBID : PMC:4296168

Descripteurs français

English descriptors

KwdEn :
- Aged, Aged, 80 and over, Apolipoproteins E (genetics), Cell Adhesion Molecules (genetics), Cohort Studies, Female, Forkhead Box Protein O3, Forkhead Transcription Factors (genetics), Genome-Wide Association Study, Humans, Longevity (genetics), Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Kainic Acid (genetics).
MESH :
- chemical , genetics : Apolipoproteins E, Cell Adhesion Molecules, Forkhead Transcription Factors, Receptors, Kainic Acid.
- genetics : Longevity.
- Aged, Aged, 80 and over, Cohort Studies, Female, Forkhead Box Protein O3, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide.

Abstract

Background.

The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.

Methods.

We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.

Results.

In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10⁻⁷) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10⁻⁸) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10⁻¹⁰).

Conclusions.

We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296168

DOI: 10.1093/gerona/glu166
PubMed: 25199915
PubMed Central: 4296168

Affiliations:

Islande, Israël, Italie, Pays-Bas

Le document en format XML

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<author><name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A." last="Smith">Jennifer A. Smith</name>
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<author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V." last="Smith">Albert V. Smith</name>
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<country xml:lang="fr">Islande</country>
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<affiliation><nlm:aff id="AF0012"><institution>Department of Medicine, University of Iceland</institution>
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<author><name sortKey="Tanaka, Toshiko" sort="Tanaka, Toshiko" uniqKey="Tanaka T" first="Toshiko" last="Tanaka">Toshiko Tanaka</name>
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<author><name sortKey="Yu, Lei" sort="Yu, Lei" uniqKey="Yu L" first="Lei" last="Yu">Lei Yu</name>
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<author><name sortKey="Arnold, Alice M" sort="Arnold, Alice M" uniqKey="Arnold A" first="Alice M." last="Arnold">Alice M. Arnold</name>
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.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Aspelund, Thor" sort="Aspelund, Thor" uniqKey="Aspelund T" first="Thor" last="Aspelund">Thor Aspelund</name>
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,<addr-line>Kopavogur</addr-line>
,<country>Iceland</country>
.</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="AF0012"><institution>Department of Medicine, University of Iceland</institution>
,<addr-line>Reykjavik</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Benjamin, Emelia J" sort="Benjamin, Emelia J" uniqKey="Benjamin E" first="Emelia J." last="Benjamin">Emelia J. Benjamin</name>
<affiliation><nlm:aff id="AF0009"><institution>NHLBI’s and Boston Univesity’s Framingham Heart Study</institution>
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</affiliation>
<affiliation><nlm:aff id="AF0015"><institution>Department of Medicine, Sections of Preventive Medicine and Cardiology, Boston University School of Medicine</institution>
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.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0016"><institution>Department of Epidemiology, Boston University School of Public Health</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
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<author><name sortKey="De Jager, Philip L" sort="De Jager, Philip L" uniqKey="De Jager P" first="Philip L." last="De Jager">Philip L. De Jager</name>
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<affiliation><nlm:aff id="AF0018"><institution>Harvard Medical School</institution>
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</affiliation>
<affiliation><nlm:aff id="AF0019"><institution>Program in Medical and Population Genetics, Broad Institute</institution>
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</author>
<author><name sortKey="Eirkisdottir, Gudny" sort="Eirkisdottir, Gudny" uniqKey="Eirkisdottir G" first="Gudny" last="Eirkisdottir">Gudny Eirkisdottir</name>
<affiliation wicri:level="1"><nlm:aff id="AF0011"><institution>Icelandic Heart Association</institution>
,<addr-line>Kopavogur</addr-line>
,<country>Iceland</country>
.</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Evans, Denis A" sort="Evans, Denis A" uniqKey="Evans D" first="Denis A." last="Evans">Denis A. Evans</name>
<affiliation><nlm:aff id="AF0020"><institution>Rush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center</institution>
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.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Garcia, Melissa E" sort="Garcia, Melissa E" uniqKey="Garcia M" first="Melissa E." last="Garcia">Melissa E. Garcia</name>
<affiliation><nlm:aff id="AF0021"><institution>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</institution>
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</affiliation>
</author>
<author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
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.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Kaplan, Robert C" sort="Kaplan, Robert C" uniqKey="Kaplan R" first="Robert C." last="Kaplan">Robert C. Kaplan</name>
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</affiliation>
</author>
<author><name sortKey="Kardia, Sharon L R" sort="Kardia, Sharon L R" uniqKey="Kardia S" first="Sharon L. R." last="Kardia">Sharon L. R. Kardia</name>
<affiliation><nlm:aff id="AF0010"><institution>Department of Epidemiology, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kiel, Douglas P" sort="Kiel, Douglas P" uniqKey="Kiel D" first="Douglas P." last="Kiel">Douglas P. Kiel</name>
<affiliation><nlm:aff id="AF0018"><institution>Harvard Medical School</institution>
,<addr-line>Boston, Massachusetts.</addr-line>
</nlm:aff>
<wicri:noCountry code="subfield">Massachusetts.</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="AF0023"><institution>Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School Department of Medicine</institution>
,<addr-line>Boston, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0024"><institution>Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center</institution>
,<addr-line>Boston, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A." last="Oostra">Ben A. Oostra</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Orwoll, Eric S" sort="Orwoll, Eric S" uniqKey="Orwoll E" first="Eric S." last="Orwoll">Eric S. Orwoll</name>
<affiliation><nlm:aff id="AF0025"><institution>School of Medicine, Oregon Health and Science University</institution>
,<addr-line>Portland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Parimi, Neeta" sort="Parimi, Neeta" uniqKey="Parimi N" first="Neeta" last="Parimi">Neeta Parimi</name>
<affiliation><nlm:aff id="AF0006"><institution>California Pacific Medical Center Research Institute</institution>
,<addr-line>San Francisco</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M." last="Psaty">Bruce M. Psaty</name>
<affiliation><nlm:aff id="AF0026"><institution>Department of Medicine, University of Washington</institution>
,<addr-line>Seattle</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0027"><institution>Deparment of Epidemiology, University of Washington</institution>
,<addr-line>Seattle</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0028"><institution>Department of Health Services, University of Washington</institution>
,<addr-line>Seattle</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0029"><institution>Group Health Research Institute, Group Health Cooperative</institution>
,<addr-line>Seattle, Washington</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I." last="Rotter">Jerome I. Rotter</name>
<affiliation><nlm:aff id="AF0030"><institution>Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center</institution>
,<addr-line>Torrance, California</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name>
<affiliation><nlm:aff id="AF0008"><institution>Department of Biostatistics, Boston University School of Public Health</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0031"><institution>Department of Neurology, Boston University School of Medicine</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
<affiliation><nlm:aff id="AF0032"><institution>Laboratory of Neurogenetics, National Institute on Aging</institution>
,<addr-line>Bethesda, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tiemeier, Henning" sort="Tiemeier, Henning" uniqKey="Tiemeier H" first="Henning" last="Tiemeier">Henning Tiemeier</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
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.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0033"><institution>Department of Child and Adolescent Psychiatry, Erasmus MC and Sophia Children’s Hospital</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G." last="Uitterlinden">André G. Uitterlinden</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Department of Internal Medicine, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhao, Wei" sort="Zhao, Wei" uniqKey="Zhao W" first="Wei" last="Zhao">Wei Zhao</name>
<affiliation><nlm:aff id="AF0010"><institution>Department of Epidemiology, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bandinelli, Stefania" sort="Bandinelli, Stefania" uniqKey="Bandinelli S" first="Stefania" last="Bandinelli">Stefania Bandinelli</name>
<affiliation wicri:level="1"><nlm:aff id="AF0034"><institution>Geriatric Unit, Azienda Sanitaria Firenze</institution>
,<addr-line>Florence</addr-line>
,<country>Italy</country>
.</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A." last="Bennett">David A. Bennett</name>
<affiliation><nlm:aff id="AF0035"><institution>Rush Alzheimer’s Disease Center, Rush University Medical Center</institution>
,<addr-line>Chicago, Illinois</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ferrucci, Luigi" sort="Ferrucci, Luigi" uniqKey="Ferrucci L" first="Luigi" last="Ferrucci">Luigi Ferrucci</name>
<affiliation><nlm:aff id="AF0013"><institution>Translational Gerontology Branch, National Institute on Aging</institution>
,<addr-line>Baltimore, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name>
<affiliation wicri:level="1"><nlm:aff id="AF0011"><institution>Icelandic Heart Association</institution>
,<addr-line>Kopavogur</addr-line>
,<country>Iceland</country>
.</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="AF0012"><institution>Department of Medicine, University of Iceland</institution>
,<addr-line>Reykjavik</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name>
<affiliation><nlm:aff id="AF0021"><institution>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</institution>
,<addr-line>Bethesda, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Karasik, David" sort="Karasik, David" uniqKey="Karasik D" first="David" last="Karasik">David Karasik</name>
<affiliation><nlm:aff id="AF0023"><institution>Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School Department of Medicine</institution>
,<addr-line>Boston, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0036"><institution>Faculty of Medicine in The Galilee, Bar-Ilan University</institution>
,<addr-line>Safed</addr-line>
,<country>Israel</country>
.</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J." last="Launer">Lenore J. Launer</name>
<affiliation><nlm:aff id="AF0021"><institution>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</institution>
,<addr-line>Bethesda, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Perls, Thomas T" sort="Perls, Thomas T" uniqKey="Perls T" first="Thomas T." last="Perls">Thomas T. Perls</name>
<affiliation><nlm:aff id="AF0037"><institution>Section of Geriatrics, Boston University School of Medicine and Boston Medical Center</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P. Eline" last="Slagboom">P. Eline Slagboom</name>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0005"><institution>Department of Molecular Epidemiology, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tranah, Gregory J" sort="Tranah, Gregory J" uniqKey="Tranah G" first="Gregory J." last="Tranah">Gregory J. Tranah</name>
<affiliation><nlm:aff id="AF0006"><institution>California Pacific Medical Center Research Institute</institution>
,<addr-line>San Francisco</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0038"><institution>Department of Epidemiology and Biostatistics, University of California</institution>
,<addr-line>San Francisco</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Weir, David R" sort="Weir, David R" uniqKey="Weir D" first="David R." last="Weir">David R. Weir</name>
<affiliation><nlm:aff id="AF0007"><institution>Survey Research Center, Institute for Social Research, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Newman, Anne B" sort="Newman, Anne B" uniqKey="Newman A" first="Anne B." last="Newman">Anne B. Newman</name>
<affiliation><nlm:aff id="AF0039"><institution>Department of Epidemiology, University of Pittsburgh</institution>
,<addr-line>Pennsylvania</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0041"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M." last="Van Duijn">Cornelia M. Van Duijn</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="AF0041"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Murabito, Joanne M" sort="Murabito, Joanne M" uniqKey="Murabito J" first="Joanne M." last="Murabito">Joanne M. Murabito</name>
<affiliation><nlm:aff id="AF0009"><institution>NHLBI’s and Boston Univesity’s Framingham Heart Study</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0040"><institution>Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0041"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25199915</idno>
<idno type="pmc">4296168</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296168</idno>
<idno type="RBID">PMC:4296168</idno>
<idno type="doi">10.1093/gerona/glu166</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000A87</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A87</idno>
<idno type="wicri:Area/Pmc/Curation">000A62</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A62</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001248</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001248</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">000897</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000897</idno>
<idno type="wicri:Area/PubMed/Curation">000897</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000897</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000897</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000897</idno>
<idno type="wicri:Area/Ncbi/Merge">003428</idno>
<idno type="wicri:Area/Ncbi/Curation">003428</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003428</idno>
<idno type="wicri:doubleKey">1079-5006:2014:Broer L:gwas:of:longevity</idno>
<idno type="wicri:Area/Main/Merge">002D96</idno>
<idno type="wicri:Area/Main/Curation">002C67</idno>
<idno type="wicri:Area/Main/Exploration">002C67</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">GWAS of Longevity in CHARGE Consortium Confirms <italic>APOE</italic>
 and <italic>FOXO3</italic>
 Candidacy</title>
<author><name sortKey="Broer, Linda" sort="Broer, Linda" uniqKey="Broer L" first="Linda" last="Broer">Linda Broer</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Department of Internal Medicine, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Buchman, Aron S" sort="Buchman, Aron S" uniqKey="Buchman A" first="Aron S." last="Buchman">Aron S. Buchman</name>
<affiliation><nlm:aff id="AF0004"><institution>Rush Alzheimer’s Disease Center, Rush University Medical Center</institution>
,<addr-line>Chicago</addr-line>
,<country>Illinois</country>
.</nlm:aff>
<wicri:noCountry code="nlm country">Illinois</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Deelen, Joris" sort="Deelen, Joris" uniqKey="Deelen J" first="Joris" last="Deelen">Joris Deelen</name>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0005"><institution>Department of Molecular Epidemiology, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Evans, Daniel S" sort="Evans, Daniel S" uniqKey="Evans D" first="Daniel S." last="Evans">Daniel S. Evans</name>
<affiliation><nlm:aff id="AF0006"><institution>California Pacific Medical Center Research Institute</institution>
,<addr-line>San Francisco</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Faul, Jessica D" sort="Faul, Jessica D" uniqKey="Faul J" first="Jessica D." last="Faul">Jessica D. Faul</name>
<affiliation><nlm:aff id="AF0007"><institution>Survey Research Center, Institute for Social Research, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lunetta, Kathryn L" sort="Lunetta, Kathryn L" uniqKey="Lunetta K" first="Kathryn L." last="Lunetta">Kathryn L. Lunetta</name>
<affiliation><nlm:aff id="AF0008"><institution>Department of Biostatistics, Boston University School of Public Health</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0009"><institution>NHLBI’s and Boston Univesity’s Framingham Heart Study</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sebastiani, Paola" sort="Sebastiani, Paola" uniqKey="Sebastiani P" first="Paola" last="Sebastiani">Paola Sebastiani</name>
<affiliation><nlm:aff id="AF0008"><institution>Department of Biostatistics, Boston University School of Public Health</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A." last="Smith">Jennifer A. Smith</name>
<affiliation><nlm:aff id="AF0010"><institution>Department of Epidemiology, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V." last="Smith">Albert V. Smith</name>
<affiliation wicri:level="1"><nlm:aff id="AF0011"><institution>Icelandic Heart Association</institution>
,<addr-line>Kopavogur</addr-line>
,<country>Iceland</country>
.</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="AF0012"><institution>Department of Medicine, University of Iceland</institution>
,<addr-line>Reykjavik</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tanaka, Toshiko" sort="Tanaka, Toshiko" uniqKey="Tanaka T" first="Toshiko" last="Tanaka">Toshiko Tanaka</name>
<affiliation><nlm:aff id="AF0013"><institution>Translational Gerontology Branch, National Institute on Aging</institution>
,<addr-line>Baltimore, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yu, Lei" sort="Yu, Lei" uniqKey="Yu L" first="Lei" last="Yu">Lei Yu</name>
<affiliation><nlm:aff id="AF0004"><institution>Rush Alzheimer’s Disease Center, Rush University Medical Center</institution>
,<addr-line>Chicago</addr-line>
,<country>Illinois</country>
.</nlm:aff>
<wicri:noCountry code="nlm country">Illinois</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Arnold, Alice M" sort="Arnold, Alice M" uniqKey="Arnold A" first="Alice M." last="Arnold">Alice M. Arnold</name>
<affiliation><nlm:aff id="AF0014"><institution>Department of Biostatistics, University of Washington</institution>
,<addr-line>Seattle</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Aspelund, Thor" sort="Aspelund, Thor" uniqKey="Aspelund T" first="Thor" last="Aspelund">Thor Aspelund</name>
<affiliation wicri:level="1"><nlm:aff id="AF0011"><institution>Icelandic Heart Association</institution>
,<addr-line>Kopavogur</addr-line>
,<country>Iceland</country>
.</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="AF0012"><institution>Department of Medicine, University of Iceland</institution>
,<addr-line>Reykjavik</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Benjamin, Emelia J" sort="Benjamin, Emelia J" uniqKey="Benjamin E" first="Emelia J." last="Benjamin">Emelia J. Benjamin</name>
<affiliation><nlm:aff id="AF0009"><institution>NHLBI’s and Boston Univesity’s Framingham Heart Study</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0015"><institution>Department of Medicine, Sections of Preventive Medicine and Cardiology, Boston University School of Medicine</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0016"><institution>Department of Epidemiology, Boston University School of Public Health</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="De Jager, Philip L" sort="De Jager, Philip L" uniqKey="De Jager P" first="Philip L." last="De Jager">Philip L. De Jager</name>
<affiliation><nlm:aff id="AF0017"><institution>Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women’s Hospital</institution>
,<addr-line>Boston, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0018"><institution>Harvard Medical School</institution>
,<addr-line>Boston, Massachusetts.</addr-line>
</nlm:aff>
<wicri:noCountry code="subfield">Massachusetts.</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="AF0019"><institution>Program in Medical and Population Genetics, Broad Institute</institution>
,<addr-line>Cambridge, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Eirkisdottir, Gudny" sort="Eirkisdottir, Gudny" uniqKey="Eirkisdottir G" first="Gudny" last="Eirkisdottir">Gudny Eirkisdottir</name>
<affiliation wicri:level="1"><nlm:aff id="AF0011"><institution>Icelandic Heart Association</institution>
,<addr-line>Kopavogur</addr-line>
,<country>Iceland</country>
.</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Evans, Denis A" sort="Evans, Denis A" uniqKey="Evans D" first="Denis A." last="Evans">Denis A. Evans</name>
<affiliation><nlm:aff id="AF0020"><institution>Rush Institute for Healthy Aging and Department of Internal Medicine, Rush University Medical Center</institution>
,<addr-line>Chicago, Illinois</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Garcia, Melissa E" sort="Garcia, Melissa E" uniqKey="Garcia M" first="Melissa E." last="Garcia">Melissa E. Garcia</name>
<affiliation><nlm:aff id="AF0021"><institution>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</institution>
,<addr-line>Bethesda, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kaplan, Robert C" sort="Kaplan, Robert C" uniqKey="Kaplan R" first="Robert C." last="Kaplan">Robert C. Kaplan</name>
<affiliation><nlm:aff id="AF0022"><institution>Department of Epidemiology and Population Health, Albert Einstein College</institution>
,<addr-line>Bronx, New York</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kardia, Sharon L R" sort="Kardia, Sharon L R" uniqKey="Kardia S" first="Sharon L. R." last="Kardia">Sharon L. R. Kardia</name>
<affiliation><nlm:aff id="AF0010"><institution>Department of Epidemiology, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kiel, Douglas P" sort="Kiel, Douglas P" uniqKey="Kiel D" first="Douglas P." last="Kiel">Douglas P. Kiel</name>
<affiliation><nlm:aff id="AF0018"><institution>Harvard Medical School</institution>
,<addr-line>Boston, Massachusetts.</addr-line>
</nlm:aff>
<wicri:noCountry code="subfield">Massachusetts.</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="AF0023"><institution>Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School Department of Medicine</institution>
,<addr-line>Boston, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0024"><institution>Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center</institution>
,<addr-line>Boston, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A." last="Oostra">Ben A. Oostra</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Orwoll, Eric S" sort="Orwoll, Eric S" uniqKey="Orwoll E" first="Eric S." last="Orwoll">Eric S. Orwoll</name>
<affiliation><nlm:aff id="AF0025"><institution>School of Medicine, Oregon Health and Science University</institution>
,<addr-line>Portland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Parimi, Neeta" sort="Parimi, Neeta" uniqKey="Parimi N" first="Neeta" last="Parimi">Neeta Parimi</name>
<affiliation><nlm:aff id="AF0006"><institution>California Pacific Medical Center Research Institute</institution>
,<addr-line>San Francisco</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M." last="Psaty">Bruce M. Psaty</name>
<affiliation><nlm:aff id="AF0026"><institution>Department of Medicine, University of Washington</institution>
,<addr-line>Seattle</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0027"><institution>Deparment of Epidemiology, University of Washington</institution>
,<addr-line>Seattle</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0028"><institution>Department of Health Services, University of Washington</institution>
,<addr-line>Seattle</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0029"><institution>Group Health Research Institute, Group Health Cooperative</institution>
,<addr-line>Seattle, Washington</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff>NONE</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I." last="Rotter">Jerome I. Rotter</name>
<affiliation><nlm:aff id="AF0030"><institution>Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center</institution>
,<addr-line>Torrance, California</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name>
<affiliation><nlm:aff id="AF0008"><institution>Department of Biostatistics, Boston University School of Public Health</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0031"><institution>Department of Neurology, Boston University School of Medicine</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
<affiliation><nlm:aff id="AF0032"><institution>Laboratory of Neurogenetics, National Institute on Aging</institution>
,<addr-line>Bethesda, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Tiemeier, Henning" sort="Tiemeier, Henning" uniqKey="Tiemeier H" first="Henning" last="Tiemeier">Henning Tiemeier</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0033"><institution>Department of Child and Adolescent Psychiatry, Erasmus MC and Sophia Children’s Hospital</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G." last="Uitterlinden">André G. Uitterlinden</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0003"><institution>Department of Internal Medicine, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhao, Wei" sort="Zhao, Wei" uniqKey="Zhao W" first="Wei" last="Zhao">Wei Zhao</name>
<affiliation><nlm:aff id="AF0010"><institution>Department of Epidemiology, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bandinelli, Stefania" sort="Bandinelli, Stefania" uniqKey="Bandinelli S" first="Stefania" last="Bandinelli">Stefania Bandinelli</name>
<affiliation wicri:level="1"><nlm:aff id="AF0034"><institution>Geriatric Unit, Azienda Sanitaria Firenze</institution>
,<addr-line>Florence</addr-line>
,<country>Italy</country>
.</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A." last="Bennett">David A. Bennett</name>
<affiliation><nlm:aff id="AF0035"><institution>Rush Alzheimer’s Disease Center, Rush University Medical Center</institution>
,<addr-line>Chicago, Illinois</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ferrucci, Luigi" sort="Ferrucci, Luigi" uniqKey="Ferrucci L" first="Luigi" last="Ferrucci">Luigi Ferrucci</name>
<affiliation><nlm:aff id="AF0013"><institution>Translational Gerontology Branch, National Institute on Aging</institution>
,<addr-line>Baltimore, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name>
<affiliation wicri:level="1"><nlm:aff id="AF0011"><institution>Icelandic Heart Association</institution>
,<addr-line>Kopavogur</addr-line>
,<country>Iceland</country>
.</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="AF0012"><institution>Department of Medicine, University of Iceland</institution>
,<addr-line>Reykjavik</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name>
<affiliation><nlm:aff id="AF0021"><institution>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</institution>
,<addr-line>Bethesda, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Karasik, David" sort="Karasik, David" uniqKey="Karasik D" first="David" last="Karasik">David Karasik</name>
<affiliation><nlm:aff id="AF0023"><institution>Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School Department of Medicine</institution>
,<addr-line>Boston, Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0036"><institution>Faculty of Medicine in The Galilee, Bar-Ilan University</institution>
,<addr-line>Safed</addr-line>
,<country>Israel</country>
.</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J." last="Launer">Lenore J. Launer</name>
<affiliation><nlm:aff id="AF0021"><institution>Laboratory of Epidemiology and Population Sciences, National Institute on Aging</institution>
,<addr-line>Bethesda, Maryland</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Perls, Thomas T" sort="Perls, Thomas T" uniqKey="Perls T" first="Thomas T." last="Perls">Thomas T. Perls</name>
<affiliation><nlm:aff id="AF0037"><institution>Section of Geriatrics, Boston University School of Medicine and Boston Medical Center</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P. Eline" last="Slagboom">P. Eline Slagboom</name>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0005"><institution>Department of Molecular Epidemiology, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tranah, Gregory J" sort="Tranah, Gregory J" uniqKey="Tranah G" first="Gregory J." last="Tranah">Gregory J. Tranah</name>
<affiliation><nlm:aff id="AF0006"><institution>California Pacific Medical Center Research Institute</institution>
,<addr-line>San Francisco</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0038"><institution>Department of Epidemiology and Biostatistics, University of California</institution>
,<addr-line>San Francisco</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Weir, David R" sort="Weir, David R" uniqKey="Weir D" first="David R." last="Weir">David R. Weir</name>
<affiliation><nlm:aff id="AF0007"><institution>Survey Research Center, Institute for Social Research, University of Michigan</institution>
,<addr-line>Ann Arbor</addr-line>
.</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Newman, Anne B" sort="Newman, Anne B" uniqKey="Newman A" first="Anne B." last="Newman">Anne B. Newman</name>
<affiliation><nlm:aff id="AF0039"><institution>Department of Epidemiology, University of Pittsburgh</institution>
,<addr-line>Pennsylvania</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0041"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M." last="Van Duijn">Cornelia M. Van Duijn</name>
<affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Department of Epidemiology, Erasmus MC</institution>
,<addr-line>Rotterdam</addr-line>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Netherlands Consortium for Healthy Ageing, Leiden University Medical Center</institution>
,<country>The Netherlands</country>
.</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="AF0041"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Murabito, Joanne M" sort="Murabito, Joanne M" uniqKey="Murabito J" first="Joanne M." last="Murabito">Joanne M. Murabito</name>
<affiliation><nlm:aff id="AF0009"><institution>NHLBI’s and Boston Univesity’s Framingham Heart Study</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0040"><institution>Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine</institution>
,<addr-line>Massachusetts</addr-line>
.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0041"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journals of Gerontology Series A: Biological Sciences and Medical Sciences</title>
<idno type="ISSN">1079-5006</idno>
<idno type="eISSN">1758-535X</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Apolipoproteins E (genetics)</term>
<term>Cell Adhesion Molecules (genetics)</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Forkhead Box Protein O3</term>
<term>Forkhead Transcription Factors (genetics)</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Longevity (genetics)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Receptors, Kainic Acid (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term>
<term>Apolipoprotéines E (génétique)</term>
<term>Facteurs de transcription Forkhead (génétique)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Longévité (génétique)</term>
<term>Molécules d'adhérence cellulaire (génétique)</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Protéine O3 à motif en tête de fourche</term>
<term>Récepteurs kaïnate (génétique)</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Étude d'association pangénomique</term>
<term>Études de cohortes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Apolipoproteins E</term>
<term>Cell Adhesion Molecules</term>
<term>Forkhead Transcription Factors</term>
<term>Receptors, Kainic Acid</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Longevity</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Apolipoprotéines E</term>
<term>Facteurs de transcription Forkhead</term>
<term>Longévité</term>
<term>Molécules d'adhérence cellulaire</term>
<term>Récepteurs kaïnate</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Forkhead Box Protein O3</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Protéine O3 à motif en tête de fourche</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Étude d'association pangénomique</term>
<term>Études de cohortes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background.</title>
<p>The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, <italic>APOE</italic>
 and <italic>FOXO3</italic>
, have shown association with longevity in multiple independent studies.</p>
</sec>
<sec><title>Methods.</title>
<p>We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.</p>
</sec>
<sec><title>Results.</title>
<p>In our meta-analysis, we found suggestive evidence for the association of SNPs near <italic>CADM2</italic>
 (odds ratio [OR] = 0.81; <italic>p</italic>
 value = 9.66 × 10<sup>−7</sup>
) and <italic>GRIK2</italic>
 (odds ratio = 1.24; <italic>p</italic>
 value = 5.09 × 10<sup>−8</sup>
) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the <italic>APOE</italic>
 locus consistently replicated. In an additional look-up of the candidate gene <italic>FOXO3</italic>
, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; <italic>p</italic>
 value = 1.85×10<sup>−10</sup>
).</p>
</sec>
<sec><title>Conclusions.</title>
<p>We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for <italic>APOE</italic>
 and <italic>FOXO3</italic>
. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list><country><li>Islande</li>
<li>Israël</li>
<li>Italie</li>
<li>Pays-Bas</li>
</country>
</list>
<tree><noCountry><name sortKey="Arnold, Alice M" sort="Arnold, Alice M" uniqKey="Arnold A" first="Alice M." last="Arnold">Alice M. Arnold</name>
<name sortKey="Benjamin, Emelia J" sort="Benjamin, Emelia J" uniqKey="Benjamin E" first="Emelia J." last="Benjamin">Emelia J. Benjamin</name>
<name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A." last="Bennett">David A. Bennett</name>
<name sortKey="Buchman, Aron S" sort="Buchman, Aron S" uniqKey="Buchman A" first="Aron S." last="Buchman">Aron S. Buchman</name>
<name sortKey="De Jager, Philip L" sort="De Jager, Philip L" uniqKey="De Jager P" first="Philip L." last="De Jager">Philip L. De Jager</name>
<name sortKey="Evans, Daniel S" sort="Evans, Daniel S" uniqKey="Evans D" first="Daniel S." last="Evans">Daniel S. Evans</name>
<name sortKey="Evans, Denis A" sort="Evans, Denis A" uniqKey="Evans D" first="Denis A." last="Evans">Denis A. Evans</name>
<name sortKey="Faul, Jessica D" sort="Faul, Jessica D" uniqKey="Faul J" first="Jessica D." last="Faul">Jessica D. Faul</name>
<name sortKey="Ferrucci, Luigi" sort="Ferrucci, Luigi" uniqKey="Ferrucci L" first="Luigi" last="Ferrucci">Luigi Ferrucci</name>
<name sortKey="Garcia, Melissa E" sort="Garcia, Melissa E" uniqKey="Garcia M" first="Melissa E." last="Garcia">Melissa E. Garcia</name>
<name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name>
<name sortKey="Kaplan, Robert C" sort="Kaplan, Robert C" uniqKey="Kaplan R" first="Robert C." last="Kaplan">Robert C. Kaplan</name>
<name sortKey="Kardia, Sharon L R" sort="Kardia, Sharon L R" uniqKey="Kardia S" first="Sharon L. R." last="Kardia">Sharon L. R. Kardia</name>
<name sortKey="Kiel, Douglas P" sort="Kiel, Douglas P" uniqKey="Kiel D" first="Douglas P." last="Kiel">Douglas P. Kiel</name>
<name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J." last="Launer">Lenore J. Launer</name>
<name sortKey="Lunetta, Kathryn L" sort="Lunetta, Kathryn L" uniqKey="Lunetta K" first="Kathryn L." last="Lunetta">Kathryn L. Lunetta</name>
<name sortKey="Murabito, Joanne M" sort="Murabito, Joanne M" uniqKey="Murabito J" first="Joanne M." last="Murabito">Joanne M. Murabito</name>
<name sortKey="Newman, Anne B" sort="Newman, Anne B" uniqKey="Newman A" first="Anne B." last="Newman">Anne B. Newman</name>
<name sortKey="Orwoll, Eric S" sort="Orwoll, Eric S" uniqKey="Orwoll E" first="Eric S." last="Orwoll">Eric S. Orwoll</name>
<name sortKey="Parimi, Neeta" sort="Parimi, Neeta" uniqKey="Parimi N" first="Neeta" last="Parimi">Neeta Parimi</name>
<name sortKey="Perls, Thomas T" sort="Perls, Thomas T" uniqKey="Perls T" first="Thomas T." last="Perls">Thomas T. Perls</name>
<name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M." last="Psaty">Bruce M. Psaty</name>
<name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I." last="Rotter">Jerome I. Rotter</name>
<name sortKey="Sebastiani, Paola" sort="Sebastiani, Paola" uniqKey="Sebastiani P" first="Paola" last="Sebastiani">Paola Sebastiani</name>
<name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name>
<name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
<name sortKey="Smith, Jennifer A" sort="Smith, Jennifer A" uniqKey="Smith J" first="Jennifer A." last="Smith">Jennifer A. Smith</name>
<name sortKey="Tanaka, Toshiko" sort="Tanaka, Toshiko" uniqKey="Tanaka T" first="Toshiko" last="Tanaka">Toshiko Tanaka</name>
<name sortKey="Tranah, Gregory J" sort="Tranah, Gregory J" uniqKey="Tranah G" first="Gregory J." last="Tranah">Gregory J. Tranah</name>
<name sortKey="Weir, David R" sort="Weir, David R" uniqKey="Weir D" first="David R." last="Weir">David R. Weir</name>
<name sortKey="Yu, Lei" sort="Yu, Lei" uniqKey="Yu L" first="Lei" last="Yu">Lei Yu</name>
<name sortKey="Zhao, Wei" sort="Zhao, Wei" uniqKey="Zhao W" first="Wei" last="Zhao">Wei Zhao</name>
</noCountry>
<country name="Pays-Bas"><noRegion><name sortKey="Broer, Linda" sort="Broer, Linda" uniqKey="Broer L" first="Linda" last="Broer">Linda Broer</name>
</noRegion>
<name sortKey="Broer, Linda" sort="Broer, Linda" uniqKey="Broer L" first="Linda" last="Broer">Linda Broer</name>
<name sortKey="Broer, Linda" sort="Broer, Linda" uniqKey="Broer L" first="Linda" last="Broer">Linda Broer</name>
<name sortKey="Deelen, Joris" sort="Deelen, Joris" uniqKey="Deelen J" first="Joris" last="Deelen">Joris Deelen</name>
<name sortKey="Deelen, Joris" sort="Deelen, Joris" uniqKey="Deelen J" first="Joris" last="Deelen">Joris Deelen</name>
<name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A." last="Oostra">Ben A. Oostra</name>
<name sortKey="Oostra, Ben A" sort="Oostra, Ben A" uniqKey="Oostra B" first="Ben A." last="Oostra">Ben A. Oostra</name>
<name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name>
<name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P. Eline" last="Slagboom">P. Eline Slagboom</name>
<name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P. Eline" last="Slagboom">P. Eline Slagboom</name>
<name sortKey="Tiemeier, Henning" sort="Tiemeier, Henning" uniqKey="Tiemeier H" first="Henning" last="Tiemeier">Henning Tiemeier</name>
<name sortKey="Tiemeier, Henning" sort="Tiemeier, Henning" uniqKey="Tiemeier H" first="Henning" last="Tiemeier">Henning Tiemeier</name>
<name sortKey="Tiemeier, Henning" sort="Tiemeier, Henning" uniqKey="Tiemeier H" first="Henning" last="Tiemeier">Henning Tiemeier</name>
<name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G." last="Uitterlinden">André G. Uitterlinden</name>
<name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G." last="Uitterlinden">André G. Uitterlinden</name>
<name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G." last="Uitterlinden">André G. Uitterlinden</name>
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   |texte=   GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy
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Serveur d'exploration sur Pittsburgh

GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy

GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy

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