Genome‐wide linkage analysis for human longevity: Genetics of Healthy Aging Study

Medientyp: E-Artikel
Titel: Genome‐wide linkage analysis for human longevity: Genetics of Healthy Aging Study
Beteiligte: Beekman, Marian; Blanché, Hélène; Perola, Markus; Hervonen, Anti; Bezrukov, Vladyslav; Sikora, Ewa; Flachsbart, Friederike; Christiansen, Lene; De Craen, Anton J. M.; Kirkwood, Tom B. L.; Rea, Irene Maeve; Poulain, Michel; Robine, Jean‐Marie; Valensin, Silvana; Stazi, Maria Antonietta; Passarino, Giuseppe; Deiana, Luca; Gonos, Efstathios S.; Paternoster, Lavinia; Sørensen, Thorkild I. A.; Tan, Qihua; Helmer, Quinta; van den Akker, Erik B.; Deelen, Joris; [...]
Erschienen: Wiley, 2013
Erschienen in: Aging Cell
Sprache: Englisch
DOI: 10.1111/acel.12039
ISSN: 1474-9718; 1474-9726
Entstehung:
Anmerkungen:
Beschreibung: <jats:title>Summary</jats:title><jats:p>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 <jats:styled-content style="fixed-case">C</jats:styled-content>aucasian sibling pairs that have been enrolled in 15 study centers of 11 <jats:styled-content style="fixed-case">E</jats:styled-content>uropean countries as part of the <jats:styled-content style="fixed-case">G</jats:styled-content>enetics of <jats:styled-content style="fixed-case">H</jats:styled-content>ealthy <jats:styled-content style="fixed-case">A</jats:styled-content>ging (<jats:styled-content style="fixed-case">GEHA</jats:styled-content>) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (<jats:styled-content style="fixed-case">LOD</jats:styled-content> = 3.47), chromosome 17q12‐q22 (<jats:styled-content style="fixed-case">LOD</jats:styled-content> = 2.95), chromosome 19p13.3‐p13.11 (<jats:styled-content style="fixed-case">LOD</jats:styled-content> = 3.76), and chromosome 19q13.11‐q13.32 (<jats:styled-content style="fixed-case">LOD</jats:styled-content> = 3.57). To fine map these regions linked to longevity, we performed association analysis using <jats:styled-content style="fixed-case">GWAS</jats:styled-content> data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed‐effect meta‐analysis approach, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="DDBJ/EMBL/GenBank" xlink:href="rs4420638">rs4420638</jats:ext-link> at the <jats:italic><jats:styled-content style="fixed-case">TOMM</jats:styled-content>40/<jats:styled-content style="fixed-case">APOE</jats:styled-content>/<jats:styled-content style="fixed-case">APOC</jats:styled-content>1</jats:italic> gene locus showed significant association with longevity (<jats:italic>P</jats:italic>‐value = 9.6 × 10<jats:sup>−8</jats:sup>). By combined modeling of linkage and association, we showed that association of longevity with <jats:italic><jats:styled-content style="fixed-case">APOE</jats:styled-content>ε4</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">APOE</jats:styled-content>ε2</jats:italic> alleles explain the linkage at 19q13.11‐q13.32 with <jats:italic>P</jats:italic>‐value = 0.02 and <jats:italic>P</jats:italic>‐value = 1.0 × 10<jats:sup>−5</jats:sup>, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the <jats:italic><jats:styled-content style="fixed-case">APOE</jats:styled-content></jats:italic> 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.</jats:p>
Zugangsstatus: Freier Zugang

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: