Ordinal GWAS analysis of the frailty phenotype identified a novel locus at 12q22 that underscores the role of the neurological and immune systems.

Abstract

Frailty is a complex trait that significantly increases the risk for negative health consequences, including hospitalization and disability. However, the evidence regarding the genetic basis of frailty phenotype (FP) is very limited. We conducted a genome-wide association study (GWAS) on FP using the data from the Canadian Longitudinal Study on Aging (CLSA). We classified the participants as non-frail, pre-frail, and frail, and performed a GWAS utilizing the ordinal logistic regression adjusted for sex, number of chronic conditions, and 10 principal components. Several post-GWAS analyses, including cis-eQTL analyses, were conducted to investigate the potential functional significance. In total, 23,105 participants and more than 8 million imputed SNPs were included in the analysis. The average age was 63 years, and 50.35% of the participants were female. Most participants were non-frail (11,297; 48.89%) or pre-frail (10,261; 44.41%), whereas only 1547 (6.70%) were frail. One novel genomic variant (rs147311617) at the 12p22 locus was found significant at the level of genome-wide significance (p = 4.98×10