Genome-wide association study of frailty and integrative functional analysis to elucidate its relationship with aging.

Yujin Kwak, Soyoun Yang, Minju Yuk, Kwangyeon Oh, Changgyu Lee, Taehyun Lee, Hyun Jeong Kim, Boyoung Kim, Minseo Kang, Hanseul Park, Ji Min Han, Kyung Eun Lee, Zhaoming Wang, Nan Song

College of Pharmacy, Chungbuk National University, 194-21, Osongsaengmyeong-1 Ro, Heungdeok-Gu, Cheongju, Chungcheongbuk-Do, Korea.College of Pharmacy, Chungbuk National University, 194-21, Osongsaengmyeong-1 Ro, Heungdeok-Gu, Cheongju, Chungcheongbuk-Do, Korea. · pubmed

Paper

Abstract

Frailty is a clinically recognizable condition of vulnerability with aging, leading to adverse health outcomes. Previous GWASs on frailty have identified 59 susceptibility loci, although the underlying mechanisms remain unclear. We investigated the genetic determinants of frailty and biological relationship between frailty and aging genes in 14,664 middle-aged and elderly Korean participants. We performed cohort-based (KoGES and KNHANES) meta-analysis of GWAS and candidate gene approach focusing on the aging pathway, followed by functional analyses. Frailty was defined as three phenotypes based on the FRAIL scale, CHS index, and frailty index. A meta-analysis of the GWAS on frailty identified eight novel SNPs: rs73619247 (AKAP12), rs12672085 (SUGCT), rs10881815 (SH2D4B), rs1455725, rs118100642 (BANK1), rs141617066, rs10461403, and rs10499589 at suggestive significance of P < 1.00 × 10

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Research summary

The paper identifies novel genetic loci associated with frailty, which is a condition linked to aging. The study's focus on the genetic determinants of frailty and its relationship with aging pathways contributes to understanding the biological mechanisms underlying aging, making it relevant to longevity research.

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