Genome-wide association Scan of dental caries in the permanent dentition
Identifieur interne : 001E48 ( Pmc/Checkpoint ); précédent : 001E47; suivant : 001E49Genome-wide association Scan of dental caries in the permanent dentition
Auteurs : Xiaojing Wang [États-Unis] ; John R. Shaffer [États-Unis] ; Zhen Zeng [États-Unis] ; Ferdouse Begum [États-Unis] ; Alexandre R. Vieira [États-Unis] ; Jacqueline Noel [États-Unis] ; Ida Anjomshoaa [États-Unis] ; Karen T. Cuenco [États-Unis] ; Myoung-Keun Lee [États-Unis] ; James Beck [États-Unis] ; Eric Boerwinkle [États-Unis] ; Marilyn C. Cornelis [États-Unis] ; Frank B. Hu [États-Unis] ; David R. Crosslin [États-Unis] ; Cathy C. Laurie [États-Unis] ; Sarah C. Nelson [États-Unis] ; Kimberly F. Doheny [États-Unis] ; Elizabeth W. Pugh [États-Unis] ; Deborah E. Polk [États-Unis] ; Robert J. Weyant [États-Unis] ; Richard Crout [États-Unis] ; Daniel W. Mcneil [États-Unis] ; Daniel E. Weeks [États-Unis] ; Eleanor Feingold [États-Unis] ; Mary L. Marazita [États-Unis]Source :
- BMC Oral Health [ 1472-6831 ] ; 2012.
Abstract
Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults.
Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries.
Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens.
As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.
Url:
DOI: 10.1186/1472-6831-12-57
PubMed: 23259602
PubMed Central: 3574042
Affiliations:
- États-Unis
- Pennsylvanie, Washington (État)
- Pittsburgh, Seattle
- Université de Pittsburgh, Université de Washington
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<author><name sortKey="Crout, Richard" sort="Crout, Richard" uniqKey="Crout R" first="Richard" last="Crout">Richard Crout</name>
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<author><name sortKey="Weeks, Daniel E" sort="Weeks, Daniel E" uniqKey="Weeks D" first="Daniel E" last="Weeks">Daniel E. Weeks</name>
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<author><name sortKey="Feingold, Eleanor" sort="Feingold, Eleanor" uniqKey="Feingold E" first="Eleanor" last="Feingold">Eleanor Feingold</name>
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<affiliation wicri:level="4"><nlm:aff id="I4">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L" last="Marazita">Mary L. Marazita</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
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</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I3">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I14">Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I15">Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 15213, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 15213</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide association Scan of dental caries in the permanent dentition</title>
<author><name sortKey="Wang, Xiaojing" sort="Wang, Xiaojing" uniqKey="Wang X" first="Xiaojing" last="Wang">Xiaojing Wang</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shaffer, John R" sort="Shaffer, John R" uniqKey="Shaffer J" first="John R" last="Shaffer">John R. Shaffer</name>
<affiliation wicri:level="4"><nlm:aff id="I3">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
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<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zeng, Zhen" sort="Zeng, Zhen" uniqKey="Zeng Z" first="Zhen" last="Zeng">Zhen Zeng</name>
<affiliation wicri:level="4"><nlm:aff id="I3">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Begum, Ferdouse" sort="Begum, Ferdouse" uniqKey="Begum F" first="Ferdouse" last="Begum">Ferdouse Begum</name>
<affiliation wicri:level="4"><nlm:aff id="I4">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vieira, Alexandre R" sort="Vieira, Alexandre R" uniqKey="Vieira A" first="Alexandre R" last="Vieira">Alexandre R. Vieira</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I15">Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 15213, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 15213</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I16">Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Noel, Jacqueline" sort="Noel, Jacqueline" uniqKey="Noel J" first="Jacqueline" last="Noel">Jacqueline Noel</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Anjomshoaa, Ida" sort="Anjomshoaa, Ida" uniqKey="Anjomshoaa I" first="Ida" last="Anjomshoaa">Ida Anjomshoaa</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cuenco, Karen T" sort="Cuenco, Karen T" uniqKey="Cuenco K" first="Karen T" last="Cuenco">Karen T. Cuenco</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I3">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lee, Myoung Keun" sort="Lee, Myoung Keun" uniqKey="Lee M" first="Myoung-Keun" last="Lee">Myoung-Keun Lee</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Beck, James" sort="Beck, James" uniqKey="Beck J" first="James" last="Beck">James Beck</name>
<affiliation wicri:level="1"><nlm:aff id="I5">UNC School of Dentistry, North Carolina Oral Health Institute, Chapel Hill, NC, 27599, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>UNC School of Dentistry, North Carolina Oral Health Institute, Chapel Hill, NC, 27599</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name>
<affiliation wicri:level="1"><nlm:aff id="I6">IMM Center for Human Genetics and Division of Epidemiology, School of Public Health, University of Texas, Houston, Texas, 77030, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>IMM Center for Human Genetics and Division of Epidemiology, School of Public Health, University of Texas, Houston, Texas, 77030</wicri:regionArea>
<wicri:noRegion>77030</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cornelis, Marilyn C" sort="Cornelis, Marilyn C" uniqKey="Cornelis M" first="Marilyn C" last="Cornelis">Marilyn C. Cornelis</name>
<affiliation wicri:level="1"><nlm:aff id="I7">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, 02115, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, 02115</wicri:regionArea>
<wicri:noRegion>02115</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hu, Frank B" sort="Hu, Frank B" uniqKey="Hu F" first="Frank B" last="Hu">Frank B. Hu</name>
<affiliation wicri:level="1"><nlm:aff id="I7">Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, 02115, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, 02115</wicri:regionArea>
<wicri:noRegion>02115</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Crosslin, David R" sort="Crosslin, David R" uniqKey="Crosslin D" first="David R" last="Crosslin">David R. Crosslin</name>
<affiliation wicri:level="4"><nlm:aff id="I8">Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, University of Washington, Seattle, WA, 98195</wicri:regionArea>
<orgName type="university">Université de Washington</orgName>
<placeName><settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Laurie, Cathy C" sort="Laurie, Cathy C" uniqKey="Laurie C" first="Cathy C" last="Laurie">Cathy C. Laurie</name>
<affiliation wicri:level="4"><nlm:aff id="I8">Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, University of Washington, Seattle, WA, 98195</wicri:regionArea>
<orgName type="university">Université de Washington</orgName>
<placeName><settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nelson, Sarah C" sort="Nelson, Sarah C" uniqKey="Nelson S" first="Sarah C" last="Nelson">Sarah C. Nelson</name>
<affiliation wicri:level="4"><nlm:aff id="I8">Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, University of Washington, Seattle, WA, 98195</wicri:regionArea>
<orgName type="university">Université de Washington</orgName>
<placeName><settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Doheny, Kimberly F" sort="Doheny, Kimberly F" uniqKey="Doheny K" first="Kimberly F" last="Doheny">Kimberly F. Doheny</name>
<affiliation wicri:level="1"><nlm:aff id="I9">Center for Inherited Disease Research, School of Medicine, Johns Hopkins University Baltimore, Baltimore, MD, 21205, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Inherited Disease Research, School of Medicine, Johns Hopkins University Baltimore, Baltimore, MD, 21205</wicri:regionArea>
<wicri:noRegion>21205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pugh, Elizabeth W" sort="Pugh, Elizabeth W" uniqKey="Pugh E" first="Elizabeth W" last="Pugh">Elizabeth W. Pugh</name>
<affiliation wicri:level="1"><nlm:aff id="I9">Center for Inherited Disease Research, School of Medicine, Johns Hopkins University Baltimore, Baltimore, MD, 21205, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Inherited Disease Research, School of Medicine, Johns Hopkins University Baltimore, Baltimore, MD, 21205</wicri:regionArea>
<wicri:noRegion>21205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Polk, Deborah E" sort="Polk, Deborah E" uniqKey="Polk D" first="Deborah E" last="Polk">Deborah E. Polk</name>
<affiliation wicri:level="4"><nlm:aff id="I10">Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I11">Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Weyant, Robert J" sort="Weyant, Robert J" uniqKey="Weyant R" first="Robert J" last="Weyant">Robert J. Weyant</name>
<affiliation wicri:level="4"><nlm:aff id="I10">Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Crout, Richard" sort="Crout, Richard" uniqKey="Crout R" first="Richard" last="Crout">Richard Crout</name>
<affiliation wicri:level="1"><nlm:aff id="I12">Department of Periodontics, West Virginia University School of Dentistry, Morgantown, WV, 26506, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Periodontics, West Virginia University School of Dentistry, Morgantown, WV, 26506</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Mcneil, Daniel W" sort="Mcneil, Daniel W" uniqKey="Mcneil D" first="Daniel W" last="Mcneil">Daniel W. Mcneil</name>
<affiliation wicri:level="1"><nlm:aff id="I13">Dental Practice and Rural Health, West Virginia University School of Dentistry, Morgantown, WV, 26506, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Dental Practice and Rural Health, West Virginia University School of Dentistry, Morgantown, WV, 26506</wicri:regionArea>
<wicri:noRegion>26506</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Weeks, Daniel E" sort="Weeks, Daniel E" uniqKey="Weeks D" first="Daniel E" last="Weeks">Daniel E. Weeks</name>
<affiliation wicri:level="4"><nlm:aff id="I3">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I4">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Feingold, Eleanor" sort="Feingold, Eleanor" uniqKey="Feingold E" first="Eleanor" last="Feingold">Eleanor Feingold</name>
<affiliation wicri:level="4"><nlm:aff id="I3">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I4">Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L" last="Marazita">Mary L. Marazita</name>
<affiliation wicri:level="4"><nlm:aff id="I1">Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I2">Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I3">Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I14">Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="I15">Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 15213, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 15213</wicri:regionArea>
<orgName type="university">Université de Pittsburgh</orgName>
<placeName><settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
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</author>
</analytic>
<series><title level="j">BMC Oral Health</title>
<idno type="eISSN">1472-6831</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
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<profileDesc><textClass></textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults.</p>
</sec>
<sec><title>Methods</title>
<p>Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries.</p>
</sec>
<sec><title>Results</title>
<p>Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens.</p>
</sec>
<sec><title>Conclusions</title>
<p>As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article" xml:lang="en"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Oral Health</journal-id>
<journal-id journal-id-type="iso-abbrev">BMC Oral Health</journal-id>
<journal-title-group><journal-title>BMC Oral Health</journal-title>
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<issn pub-type="epub">1472-6831</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
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<article-meta><article-id pub-id-type="pmid">23259602</article-id>
<article-id pub-id-type="pmc">3574042</article-id>
<article-id pub-id-type="publisher-id">1472-6831-12-57</article-id>
<article-id pub-id-type="doi">10.1186/1472-6831-12-57</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
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<title-group><article-title>Genome-wide association Scan of dental caries in the permanent dentition</article-title>
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<email>cclaurie@u.washington.edu</email>
</contrib>
<contrib contrib-type="author" id="A16"><name><surname>Nelson</surname>
<given-names>Sarah C</given-names>
</name>
<xref ref-type="aff" rid="I8">8</xref>
<email>sarahcn@u.washington.edu</email>
</contrib>
<contrib contrib-type="author" id="A17"><name><surname>Doheny</surname>
<given-names>Kimberly F</given-names>
</name>
<xref ref-type="aff" rid="I9">9</xref>
<email>kdoheny@cidr.jhmi.edu</email>
</contrib>
<contrib contrib-type="author" id="A18"><name><surname>Pugh</surname>
<given-names>Elizabeth W</given-names>
</name>
<xref ref-type="aff" rid="I9">9</xref>
<email>epugh1@jhmi.edu</email>
</contrib>
<contrib contrib-type="author" id="A19"><name><surname>Polk</surname>
<given-names>Deborah E</given-names>
</name>
<xref ref-type="aff" rid="I10">10</xref>
<xref ref-type="aff" rid="I11">11</xref>
<email>dpolk@pitt.edu</email>
</contrib>
<contrib contrib-type="author" id="A20"><name><surname>Weyant</surname>
<given-names>Robert J</given-names>
</name>
<xref ref-type="aff" rid="I10">10</xref>
<email>rjw1@pitt.edu</email>
</contrib>
<contrib contrib-type="author" id="A21"><name><surname>Crout</surname>
<given-names>Richard</given-names>
</name>
<xref ref-type="aff" rid="I12">12</xref>
<email>rcrout@hsc.wvu.edu</email>
</contrib>
<contrib contrib-type="author" id="A22"><name><surname>McNeil</surname>
<given-names>Daniel W</given-names>
</name>
<xref ref-type="aff" rid="I13">13</xref>
<email>Daniel.McNeil@mail.wvu.edu</email>
</contrib>
<contrib contrib-type="author" id="A23"><name><surname>Weeks</surname>
<given-names>Daniel E</given-names>
</name>
<xref ref-type="aff" rid="I3">3</xref>
<xref ref-type="aff" rid="I4">4</xref>
<email>weeks@pitt.edu</email>
</contrib>
<contrib contrib-type="author" id="A24"><name><surname>Feingold</surname>
<given-names>Eleanor</given-names>
</name>
<xref ref-type="aff" rid="I3">3</xref>
<xref ref-type="aff" rid="I4">4</xref>
<email>feingold@pitt.edu</email>
</contrib>
<contrib contrib-type="author" corresp="yes" id="A25"><name><surname>Marazita</surname>
<given-names>Mary L</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<xref ref-type="aff" rid="I2">2</xref>
<xref ref-type="aff" rid="I3">3</xref>
<xref ref-type="aff" rid="I14">14</xref>
<xref ref-type="aff" rid="I15">15</xref>
<email>marazita@pitt.edu</email>
</contrib>
</contrib-group>
<aff id="I1"><label>1</label>
Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA</aff>
<aff id="I2"><label>2</label>
Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</aff>
<aff id="I3"><label>3</label>
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</aff>
<aff id="I4"><label>4</label>
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</aff>
<aff id="I5"><label>5</label>
UNC School of Dentistry, North Carolina Oral Health Institute, Chapel Hill, NC, 27599, USA</aff>
<aff id="I6"><label>6</label>
IMM Center for Human Genetics and Division of Epidemiology, School of Public Health, University of Texas, Houston, Texas, 77030, USA</aff>
<aff id="I7"><label>7</label>
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, 02115, USA</aff>
<aff id="I8"><label>8</label>
Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA</aff>
<aff id="I9"><label>9</label>
Center for Inherited Disease Research, School of Medicine, Johns Hopkins University Baltimore, Baltimore, MD, 21205, USA</aff>
<aff id="I10"><label>10</label>
Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA, 15261, USA</aff>
<aff id="I11"><label>11</label>
Department of Behavioral and Community Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA</aff>
<aff id="I12"><label>12</label>
Department of Periodontics, West Virginia University School of Dentistry, Morgantown, WV, 26506, USA</aff>
<aff id="I13"><label>13</label>
Dental Practice and Rural Health, West Virginia University School of Dentistry, Morgantown, WV, 26506, USA</aff>
<aff id="I14"><label>14</label>
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA</aff>
<aff id="I15"><label>15</label>
Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, 15213, USA</aff>
<aff id="I16"><label>16</label>
Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA</aff>
<pub-date pub-type="collection"><year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>21</day>
<month>12</month>
<year>2012</year>
</pub-date>
<volume>12</volume>
<fpage>57</fpage>
<lpage>57</lpage>
<history><date date-type="received"><day>13</day>
<month>6</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>28</day>
<month>11</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright ©2012 Wang et al.; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>Wang et al.; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://www.biomedcentral.com/1472-6831/12/57"></self-uri>
<abstract><sec><title>Background</title>
<p>Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults.</p>
</sec>
<sec><title>Methods</title>
<p>Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries.</p>
</sec>
<sec><title>Results</title>
<p>Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens.</p>
</sec>
<sec><title>Conclusions</title>
<p>As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.</p>
</sec>
</abstract>
<kwd-group><kwd>Dental caries</kwd>
<kwd>Genetics</kwd>
<kwd>Genome wide association</kwd>
<kwd>Permanent dentition</kwd>
<kwd>Genomics</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Pennsylvanie</li>
<li>Washington (État)</li>
</region>
<settlement><li>Pittsburgh</li>
<li>Seattle</li>
</settlement>
<orgName><li>Université de Pittsburgh</li>
<li>Université de Washington</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Wang, Xiaojing" sort="Wang, Xiaojing" uniqKey="Wang X" first="Xiaojing" last="Wang">Xiaojing Wang</name>
</region>
<name sortKey="Anjomshoaa, Ida" sort="Anjomshoaa, Ida" uniqKey="Anjomshoaa I" first="Ida" last="Anjomshoaa">Ida Anjomshoaa</name>
<name sortKey="Anjomshoaa, Ida" sort="Anjomshoaa, Ida" uniqKey="Anjomshoaa I" first="Ida" last="Anjomshoaa">Ida Anjomshoaa</name>
<name sortKey="Beck, James" sort="Beck, James" uniqKey="Beck J" first="James" last="Beck">James Beck</name>
<name sortKey="Begum, Ferdouse" sort="Begum, Ferdouse" uniqKey="Begum F" first="Ferdouse" last="Begum">Ferdouse Begum</name>
<name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name>
<name sortKey="Cornelis, Marilyn C" sort="Cornelis, Marilyn C" uniqKey="Cornelis M" first="Marilyn C" last="Cornelis">Marilyn C. Cornelis</name>
<name sortKey="Crosslin, David R" sort="Crosslin, David R" uniqKey="Crosslin D" first="David R" last="Crosslin">David R. Crosslin</name>
<name sortKey="Crout, Richard" sort="Crout, Richard" uniqKey="Crout R" first="Richard" last="Crout">Richard Crout</name>
<name sortKey="Cuenco, Karen T" sort="Cuenco, Karen T" uniqKey="Cuenco K" first="Karen T" last="Cuenco">Karen T. Cuenco</name>
<name sortKey="Cuenco, Karen T" sort="Cuenco, Karen T" uniqKey="Cuenco K" first="Karen T" last="Cuenco">Karen T. Cuenco</name>
<name sortKey="Cuenco, Karen T" sort="Cuenco, Karen T" uniqKey="Cuenco K" first="Karen T" last="Cuenco">Karen T. Cuenco</name>
<name sortKey="Doheny, Kimberly F" sort="Doheny, Kimberly F" uniqKey="Doheny K" first="Kimberly F" last="Doheny">Kimberly F. Doheny</name>
<name sortKey="Feingold, Eleanor" sort="Feingold, Eleanor" uniqKey="Feingold E" first="Eleanor" last="Feingold">Eleanor Feingold</name>
<name sortKey="Feingold, Eleanor" sort="Feingold, Eleanor" uniqKey="Feingold E" first="Eleanor" last="Feingold">Eleanor Feingold</name>
<name sortKey="Hu, Frank B" sort="Hu, Frank B" uniqKey="Hu F" first="Frank B" last="Hu">Frank B. Hu</name>
<name sortKey="Laurie, Cathy C" sort="Laurie, Cathy C" uniqKey="Laurie C" first="Cathy C" last="Laurie">Cathy C. Laurie</name>
<name sortKey="Lee, Myoung Keun" sort="Lee, Myoung Keun" uniqKey="Lee M" first="Myoung-Keun" last="Lee">Myoung-Keun Lee</name>
<name sortKey="Lee, Myoung Keun" sort="Lee, Myoung Keun" uniqKey="Lee M" first="Myoung-Keun" last="Lee">Myoung-Keun Lee</name>
<name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L" last="Marazita">Mary L. Marazita</name>
<name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L" last="Marazita">Mary L. Marazita</name>
<name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L" last="Marazita">Mary L. Marazita</name>
<name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L" last="Marazita">Mary L. Marazita</name>
<name sortKey="Marazita, Mary L" sort="Marazita, Mary L" uniqKey="Marazita M" first="Mary L" last="Marazita">Mary L. Marazita</name>
<name sortKey="Mcneil, Daniel W" sort="Mcneil, Daniel W" uniqKey="Mcneil D" first="Daniel W" last="Mcneil">Daniel W. Mcneil</name>
<name sortKey="Nelson, Sarah C" sort="Nelson, Sarah C" uniqKey="Nelson S" first="Sarah C" last="Nelson">Sarah C. Nelson</name>
<name sortKey="Noel, Jacqueline" sort="Noel, Jacqueline" uniqKey="Noel J" first="Jacqueline" last="Noel">Jacqueline Noel</name>
<name sortKey="Noel, Jacqueline" sort="Noel, Jacqueline" uniqKey="Noel J" first="Jacqueline" last="Noel">Jacqueline Noel</name>
<name sortKey="Polk, Deborah E" sort="Polk, Deborah E" uniqKey="Polk D" first="Deborah E" last="Polk">Deborah E. Polk</name>
<name sortKey="Polk, Deborah E" sort="Polk, Deborah E" uniqKey="Polk D" first="Deborah E" last="Polk">Deborah E. Polk</name>
<name sortKey="Pugh, Elizabeth W" sort="Pugh, Elizabeth W" uniqKey="Pugh E" first="Elizabeth W" last="Pugh">Elizabeth W. Pugh</name>
<name sortKey="Shaffer, John R" sort="Shaffer, John R" uniqKey="Shaffer J" first="John R" last="Shaffer">John R. Shaffer</name>
<name sortKey="Vieira, Alexandre R" sort="Vieira, Alexandre R" uniqKey="Vieira A" first="Alexandre R" last="Vieira">Alexandre R. Vieira</name>
<name sortKey="Vieira, Alexandre R" sort="Vieira, Alexandre R" uniqKey="Vieira A" first="Alexandre R" last="Vieira">Alexandre R. Vieira</name>
<name sortKey="Vieira, Alexandre R" sort="Vieira, Alexandre R" uniqKey="Vieira A" first="Alexandre R" last="Vieira">Alexandre R. Vieira</name>
<name sortKey="Vieira, Alexandre R" sort="Vieira, Alexandre R" uniqKey="Vieira A" first="Alexandre R" last="Vieira">Alexandre R. Vieira</name>
<name sortKey="Wang, Xiaojing" sort="Wang, Xiaojing" uniqKey="Wang X" first="Xiaojing" last="Wang">Xiaojing Wang</name>
<name sortKey="Weeks, Daniel E" sort="Weeks, Daniel E" uniqKey="Weeks D" first="Daniel E" last="Weeks">Daniel E. Weeks</name>
<name sortKey="Weeks, Daniel E" sort="Weeks, Daniel E" uniqKey="Weeks D" first="Daniel E" last="Weeks">Daniel E. Weeks</name>
<name sortKey="Weyant, Robert J" sort="Weyant, Robert J" uniqKey="Weyant R" first="Robert J" last="Weyant">Robert J. Weyant</name>
<name sortKey="Zeng, Zhen" sort="Zeng, Zhen" uniqKey="Zeng Z" first="Zhen" last="Zeng">Zhen Zeng</name>
</country>
</tree>
</affiliations>
</record>
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