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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Age-At-Onset Linkage Analysis in Caribbean Hispanics with Familial Late-Onset Alzheimer’s Disease</title><author><name sortKey="Lee, Joseph H" sort="Lee, Joseph H" uniqKey="Lee J" first="Joseph H." last="Lee">Joseph H. Lee</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A7">The Department of Epidemiology in the School of Public Health, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Barral, Sandra" sort="Barral, Sandra" uniqKey="Barral S" first="Sandra" last="Barral">Sandra Barral</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Cheng, Rong" sort="Cheng, Rong" uniqKey="Cheng R" first="Rong" last="Cheng">Rong Cheng</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Chacon, Inara" sort="Chacon, Inara" uniqKey="Chacon I" first="Inara" last="Chacon">Inara Chacon</name><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Santana, Vincent" sort="Santana, Vincent" uniqKey="Santana V" first="Vincent" last="Santana">Vincent Santana</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Williamson, Jennifer" sort="Williamson, Jennifer" uniqKey="Williamson J" first="Jennifer" last="Williamson">Jennifer Williamson</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Lantigua, Rafael" sort="Lantigua, Rafael" uniqKey="Lantigua R" first="Rafael" last="Lantigua">Rafael Lantigua</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A5">The Department of Medicine in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Medrano, Martin" sort="Medrano, Martin" uniqKey="Medrano M" first="Martin" last="Medrano">Martin Medrano</name><affiliation><nlm:aff id="A8">The Universidad Tecnologica de Santiago in the Dominican Republic</nlm:aff></affiliation></author><author><name sortKey="Jimenez Velazquez, Ivonne Z" sort="Jimenez Velazquez, Ivonne Z" uniqKey="Jimenez Velazquez I" first="Ivonne Z." last="Jimenez-Velazquez">Ivonne Z. Jimenez-Velazquez</name><affiliation><nlm:aff id="A9">The Department of Internal Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico</nlm:aff></affiliation></author><author><name sortKey="Stern, Yaakov" sort="Stern, Yaakov" uniqKey="Stern Y" first="Yaakov" last="Stern">Yaakov Stern</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A3">The Department of Neurology in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A4">The Department of Psychiatry in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Tycko, Benjamin" sort="Tycko, Benjamin" uniqKey="Tycko B" first="Benjamin" last="Tycko">Benjamin Tycko</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A6">The Department of Pathology in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="Wakutani, Yosuke" sort="Wakutani, Yosuke" uniqKey="Wakutani Y" first="Yosuke" last="Wakutani">Yosuke Wakutani</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="Kawarai, Toshitaka" sort="Kawarai, Toshitaka" uniqKey="Kawarai T" first="Toshitaka" last="Kawarai">Toshitaka Kawarai</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St George-Hyslop">Peter St George-Hyslop</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="Mayeux, Richard" sort="Mayeux, Richard" uniqKey="Mayeux R" first="Richard" last="Mayeux">Richard Mayeux</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A3">The Department of Neurology in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A4">The Department of Psychiatry in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A7">The Department of Epidemiology in the School of Public Health, Columbia University</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17940814</idno><idno type="pmc">2701253</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701253</idno><idno type="RBID">PMC:2701253</idno><idno type="doi">10.1007/s10048-007-0103-3</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000457</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000457</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Age-At-Onset Linkage Analysis in Caribbean Hispanics with Familial Late-Onset Alzheimer’s Disease</title><author><name sortKey="Lee, Joseph H" sort="Lee, Joseph H" uniqKey="Lee J" first="Joseph H." last="Lee">Joseph H. Lee</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A7">The Department of Epidemiology in the School of Public Health, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Barral, Sandra" sort="Barral, Sandra" uniqKey="Barral S" first="Sandra" last="Barral">Sandra Barral</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Cheng, Rong" sort="Cheng, Rong" uniqKey="Cheng R" first="Rong" last="Cheng">Rong Cheng</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Chacon, Inara" sort="Chacon, Inara" uniqKey="Chacon I" first="Inara" last="Chacon">Inara Chacon</name><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Santana, Vincent" sort="Santana, Vincent" uniqKey="Santana V" first="Vincent" last="Santana">Vincent Santana</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Williamson, Jennifer" sort="Williamson, Jennifer" uniqKey="Williamson J" first="Jennifer" last="Williamson">Jennifer Williamson</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Lantigua, Rafael" sort="Lantigua, Rafael" uniqKey="Lantigua R" first="Rafael" last="Lantigua">Rafael Lantigua</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A5">The Department of Medicine in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Medrano, Martin" sort="Medrano, Martin" uniqKey="Medrano M" first="Martin" last="Medrano">Martin Medrano</name><affiliation><nlm:aff id="A8">The Universidad Tecnologica de Santiago in the Dominican Republic</nlm:aff></affiliation></author><author><name sortKey="Jimenez Velazquez, Ivonne Z" sort="Jimenez Velazquez, Ivonne Z" uniqKey="Jimenez Velazquez I" first="Ivonne Z." last="Jimenez-Velazquez">Ivonne Z. Jimenez-Velazquez</name><affiliation><nlm:aff id="A9">The Department of Internal Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico</nlm:aff></affiliation></author><author><name sortKey="Stern, Yaakov" sort="Stern, Yaakov" uniqKey="Stern Y" first="Yaakov" last="Stern">Yaakov Stern</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A3">The Department of Neurology in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A4">The Department of Psychiatry in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Tycko, Benjamin" sort="Tycko, Benjamin" uniqKey="Tycko B" first="Benjamin" last="Tycko">Benjamin Tycko</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A6">The Department of Pathology in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="Wakutani, Yosuke" sort="Wakutani, Yosuke" uniqKey="Wakutani Y" first="Yosuke" last="Wakutani">Yosuke Wakutani</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="Kawarai, Toshitaka" sort="Kawarai, Toshitaka" uniqKey="Kawarai T" first="Toshitaka" last="Kawarai">Toshitaka Kawarai</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St George-Hyslop">Peter St George-Hyslop</name><affiliation><nlm:aff id="A10">Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</nlm:aff></affiliation></author><author><name sortKey="Mayeux, Richard" sort="Mayeux, Richard" uniqKey="Mayeux R" first="Richard" last="Mayeux">Richard Mayeux</name><affiliation><nlm:aff id="A1">The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A2">The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A3">The Department of Neurology in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A4">The Department of Psychiatry in the College of Physicians and Surgeons, Columbia University</nlm:aff></affiliation><affiliation><nlm:aff id="A7">The Department of Epidemiology in the School of Public Health, Columbia University</nlm:aff></affiliation></author></analytic><series><title level="j">Neurogenetics</title><idno type="ISSN">1364-6745</idno><idno type="eISSN">1364-6753</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">The aim of the study was to identify chromosomal regions containing putative genetic variants influencing age-at-onset in familial late-onset Alzheimer’s disease. Data from a genome-wide scan that included genotyping of <italic>APOE</italic> was analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age-at-onset of 73.3 years multiply affected by late-onset Alzheimer’s disease. Two-point and multipoint analyses were conducted using variance component methods from 376 microsatellite markers with an average inter-marker distance of 9.3 cM. Family-based test of association were also conducted for the same set of markers. Age-at-onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of <italic>APOE-ε4</italic> lowered the age-at-onset by three years. Using linkage analysis strategy, the highest LOD scores were obtained using a conservative definition of LOAD at 5q15 (LOD 3.1) 17q25.1 (LOD=2.94) and 14q32.12 (LOD=2.36) and 7q36.3 (LOD=2.29) in covariate adjusted models that included <italic>APOE-ε4</italic>. Both linkage and family-based association identified 17p13 as a candidate region. In addition, family-based association analysis showed markers at 12q13 (p=0.00002), 13q (p=0.00043) and 14q23 (p=0.00046) to be significantly associated with age at onset. The current study supports the hypothesis that there are additional genetic loci that could influence age-at-onset of late onset Alzheimer’s disease. The novel loci at 5q15, 17q25.1, 13q and 17p13, and the previously reported loci at 7q36.3, 12q13, 14q23 and 14q32 need further investigation.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9709714</journal-id><journal-id journal-id-type="pubmed-jr-id">20757</journal-id><journal-id journal-id-type="nlm-ta">Neurogenetics</journal-id><journal-title>Neurogenetics</journal-title><issn pub-type="ppub">1364-6745</issn><issn pub-type="epub">1364-6753</issn></journal-meta><article-meta><article-id pub-id-type="pmid">17940814</article-id><article-id pub-id-type="pmc">2701253</article-id><article-id pub-id-type="doi">10.1007/s10048-007-0103-3</article-id><article-id pub-id-type="manuscript">NIHMS88275</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Age-At-Onset Linkage Analysis in Caribbean Hispanics with Familial Late-Onset Alzheimer’s Disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Joseph H.</given-names></name><degrees>DrPH</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="author-notes" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Barral</surname><given-names>Sandra</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Rong</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Chacon</surname><given-names>Inara</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FN1">†</xref></contrib><contrib contrib-type="author"><name><surname>Santana</surname><given-names>Vincent</given-names></name><degrees>MBA</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Williamson</surname><given-names>Jennifer</given-names></name><degrees>MS</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lantigua</surname><given-names>Rafael</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Medrano</surname><given-names>Martin</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Jimenez-Velazquez</surname><given-names>Ivonne Z.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Stern</surname><given-names>Yaakov</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Tycko</surname><given-names>Benjamin</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Rogaeva</surname><given-names>Ekaterina</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Wakutani</surname><given-names>Yosuke</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Kawarai</surname><given-names>Toshitaka</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>St George-Hyslop</surname><given-names>Peter</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Mayeux</surname><given-names>Richard</given-names></name><degrees>MD, MSc</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>The Taub Institute on Alzheimer's Disease and the Aging Brain in the College of Physicians and Surgeons, Columbia University</aff><aff id="A2"><label>2</label>The Gertrude H. Sergievsky Center in the College of Physicians and Surgeons, Columbia University</aff><aff id="A3"><label>3</label>The Department of Neurology in the College of Physicians and Surgeons, Columbia University</aff><aff id="A4"><label>4</label>The Department of Psychiatry in the College of Physicians and Surgeons, Columbia University</aff><aff id="A5"><label>5</label>The Department of Medicine in the College of Physicians and Surgeons, Columbia University</aff><aff id="A6"><label>6</label>The Department of Pathology in the College of Physicians and Surgeons, Columbia University</aff><aff id="A7"><label>7</label>The Department of Epidemiology in the School of Public Health, Columbia University</aff><aff id="A8"><label>8</label>The Universidad Tecnologica de Santiago in the Dominican Republic</aff><aff id="A9"><label>9</label>The Department of Internal Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico</aff><aff id="A10"><label>10</label>Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.</aff><author-notes><fn id="FN1" fn-type="equal"><label>†</label><p id="P1">These authors contributed equally</p></fn><corresp id="cor1"><label>*</label><bold>Correspondence:</bold> Richard Mayeux, MD, MSc, Gertrude H. Sergievsky Center, 630 West 168th Street, Columbia University, New York, NY 10032. Voice: 212-305-2391, FAX: 212-305-2518, Email: <email>rpm2@columbia.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>16</day><month>1</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>17</day><month>10</month><year>2007</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2008</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>6</month><year>2009</year></pub-date><volume>9</volume><issue>1</issue><fpage>51</fpage><lpage>60</lpage><abstract><p id="P2">The aim of the study was to identify chromosomal regions containing putative genetic variants influencing age-at-onset in familial late-onset Alzheimer’s disease. Data from a genome-wide scan that included genotyping of <italic>APOE</italic> was analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age-at-onset of 73.3 years multiply affected by late-onset Alzheimer’s disease. Two-point and multipoint analyses were conducted using variance component methods from 376 microsatellite markers with an average inter-marker distance of 9.3 cM. Family-based test of association were also conducted for the same set of markers. Age-at-onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of <italic>APOE-ε4</italic> lowered the age-at-onset by three years. Using linkage analysis strategy, the highest LOD scores were obtained using a conservative definition of LOAD at 5q15 (LOD 3.1) 17q25.1 (LOD=2.94) and 14q32.12 (LOD=2.36) and 7q36.3 (LOD=2.29) in covariate adjusted models that included <italic>APOE-ε4</italic>. Both linkage and family-based association identified 17p13 as a candidate region. In addition, family-based association analysis showed markers at 12q13 (p=0.00002), 13q (p=0.00043) and 14q23 (p=0.00046) to be significantly associated with age at onset. The current study supports the hypothesis that there are additional genetic loci that could influence age-at-onset of late onset Alzheimer’s disease. The novel loci at 5q15, 17q25.1, 13q and 17p13, and the previously reported loci at 7q36.3, 12q13, 14q23 and 14q32 need further investigation.</p></abstract><kwd-group><kwd>Alzheimer’s disease</kwd><kwd>age-at-onset</kwd><kwd>linkage analysis</kwd><kwd>family-based association analysis</kwd><kwd>APOE</kwd></kwd-group><contract-num rid="AG1">R37 AG015473-11</contract-num><contract-num rid="AG1">R37 AG015473-09</contract-num><contract-num rid="AG1">R37 AG015473-08</contract-num><contract-num rid="AG1">R37 AG015473-07</contract-num><contract-num rid="AG1">R37 AG015473-06</contract-num><contract-num rid="AG1">P01 AG007232-20</contract-num><contract-sponsor id="AG1">National Institute on Aging : NIA</contract-sponsor></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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