Abstract:

Growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/insulin signaling is one of the most plausible biological pathways regulating aging and longevity. Previous studies have demonstrated that several single nucleotide polymorphisms (SNPs) in the GH/IGF-1/insulin signaling-associated genes influence both longevity and adult height, suggesting the possibility of a shared genetic architecture between longevity and height. We therefore examined the relationship between 30 height-associated SNPs and extreme longevity in a Japanese population
consisting of 428 centenarians and 4,026 younger controls. We confirmed that height-increasing genetic scores (HGSs) constructed based on 30 SNPs were significantly associated with height in the controls (p = 6.95 × 10-23). HGS was
significantly and inversely associated with extreme longevity in women (p = .011), but not in men, although no SNPs were significantly associated with extreme longevity after Bonferroni correction. The odds ratio for extreme longevity in the lowest HGS group (≤27) and the second lowest HGS group (28-30) relative to the highest HGS group (≥37) was 1.71 (p = .056) and 1.69 (p = .034),
respectively, for women. In conclusion, the present study demonstrated an inverse association between height-increasing alleles with extreme longevity in Japanese
women, providing novel insight into the genetic architecture of longevity and aging.

日本語要旨:

100歳以上の高齢者を対象にした全ゲノム解析で、身長を高くする遺伝子を有する女性は長寿になりにくいことを明らかにした。