High-density genomewide linkage analysis of exceptional human longevity identifies multiple novel loci.
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.


RESULTS
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
Our linkage data should facilitate the discovery of both common and rare variants that determine genetic variability in lifespan.
Boyden
Steven E
SE
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
Kunkel
Louis M
LM
D000369:Aged, 80 and over; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008136:Longevity / Q000235:genetics*; D008297:Male
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