Authors: Boyden SE; Kunkel LM
Abstract: BACKGROUND: Human lifespan is approximately 25% heritable, and genetic factors may be particularly important for achieving exceptional longevity. Accordingly, siblings of centenarians have a dramatically higher probability of reaching extreme old age than the general population. METHODOLOGY/PRINCIPAL FINDINGS: To map the loci conferring a survival advantage, we performed the second genomewide linkage scan on human longevity and the first using a high-density marker panel of single nucleotide polymorphisms. By systematically testing a range of minimum age cutoffs in 279 families with multiple long-lived siblings, we identified a locus on chromosome 3p24-22 with a genomewide significant allele-sharing LOD score of 4.02 (empirical P = 0.037) and a locus on chromosome 9q31-34 with a highly suggestive LOD score of 3.89 (empirical P = 0.054). The empirical P value for the combined result was 0.002. A third novel locus with a LOD score of 4.05 on chromosome 12q24 was detected in a subset of the data, and we also obtained modest evidence for a previously reported interval on chromosome 4q22-25. CONCLUSIONS/SIGNIFICANCE: Our linkage data should facilitate the discovery of both common and rare variants that determine genetic variability in lifespan.
Keywords: Aged, 80 and over; Chromosomes, Human/genetics; Female; Genetic Linkage/*genetics; Genetic Loci/*genetics; Genome, Human/*genetics; Humans; Lod Score; Longevity/*genetics; Male|
Journal: PloS one Volume: 5 Issue: 8 Pages: e12432 Date: Sept. 9, 2010 PMID: 20824210 |
Boyden SE, Kunkel LM (2010) High-density genomewide linkage analysis of exceptional human longevity identifies multiple novel loci. PloS one 5: e12432.
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