| Title: |
Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study |
| Authors: |
Beekman, M; Blanché, H; Perola, M; Hervonen, A; Bezrukov, V; Sikora, E; Flachsbart, F; Christiansen, L; de Craen, Ajm; Kirkwood, Tb; Rea, Im; Poulain, M; Robine, Jean-Marie; Valensin, S; Stazi, Ma; Passarino, G; Deiana, L; Gonos, Es; Paternoster, L; Sørensen, Ti; Tan, Q; Helmer, Q; van den Akker, Eb; Deelen, J; Martella, F; Cordell, Hj; Ayers, Kl; Vaupel, Jw; Törnwall, O; Johnson, Te; Schreiber, S; Lathrop, M; Skytthe, A; Westendorp, Rg; Christensen, K; Gampe, J; Nebel, A; Houwing-Duistermaat, Jj; Slagboom, Pe; Franceschi, C |
| Contributors: |
Leiden University Medical Center Leiden (LUMC); Universiteit Leiden = Leiden University; Fondation Jean Dausset - Centre d’Études du Polymorphisme Humain (CEPH); National Institute for Health and Welfare Helsinki; Tampere School of Public Health; Institute of Gerontology Kiev; Nencki Institute of Experimental Biology; Polska Akademia Nauk = Polish Academy of Sciences = Académie polonaise des sciences (PAN); Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel (CAU); University of Southern Denmark = Syddansk Universitet (SDU); Netherlands Consortium for Healthy Ageing; Universiteit Leiden = Leiden University-Universiteit Leiden = Leiden University; Newcastle University Newcastle; Queen's University Belfast (QUB); Université Catholique de Louvain = Catholic University of Louvain (UCL); CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7); École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Alma Mater Studiorum Università di Bologna = University of Bologna Bologne (UNIBO); Istituto Superiore di Sanità = National Institute of Health (ISS); Università della Calabria Arcavacata di Rende, Italia = University of Calabria Italy = Université de Calabre Italie (UniCal); Università degli Studi di Sassari = University of Sassari (UNISS); Theoretical and Physical Chemistry Institute NHRF; National Hellenic Research Foundation Athens; University of Bristol Bristol; Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR); Faculty of Health and Medical Sciences; Københavns Universitet = University of Copenhagen = Université de Copenhague (UCPH)-Københavns Universitet = University of Copenhagen = Université de Copenhague (UCPH); Odense University Hospital (OUH); Institute for Ageing and Health, Newcastle University; Max Planck Institute for Demographic Research (MPIDR); Max-Planck-Gesellschaft; University of Colorado Boulder |
| Source: |
ISSN: 1474-9726 ; Aging Cell ; https://cnrs.hal.science/hal-03478919 ; Aging Cell, 2013, 12 (2), pp.184-93. ⟨10.1111/acel.12039⟩. |
| Publisher Information: |
CCSD; Blackwell Publishing Ltd |
| Publication Year: |
2013 |
| Subject Terms: |
APOE gene; association analysis; genome-wide linkage analysis; Human familial longevity; nonagenarian sibling pairs; [SHS]Humanities and Social Sciences |
| Description: |
International audience ; Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD=3.47), chromosome 17q12-q22 (LOD=2.95), chromosome 19p13.3-p13.11 (LOD=3.76), and chromosome 19q13.11-q13.32 (LOD=3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P-value=9.6x108). By combined modeling of linkage and association, we showed that association of longevity with APOE epsilon 4 and APOE epsilon 2 alleles explain the linkage at 19q13.11-q13.32 with P-value=0.02 and P-value=1.0x105, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1111/acel.12039 |
| Availability: |
https://cnrs.hal.science/hal-03478919; https://cnrs.hal.science/hal-03478919v1/document; https://cnrs.hal.science/hal-03478919v1/file/Aging%20Cell%20-%202013%20-%20Beekman%20-%20Genome%E2%80%90wide%20linkage%20analysis%20for%20human%20longevity%20%20Genetics%20of%20Healthy%20Aging%20Study.pdf; https://doi.org/10.1111/acel.12039 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D21014D4 |
| Database: |
BASE |