Genetic variants associated with longevity in long-living Indians

ABSTRACT Genetic factors play a significant role in determining an individual’s longevity. The present study was aimed at identifying the genetic variants associated with longevity in Indian population. Long living individuals (LLIs), aged 85+, were compared with younger controls, aged 18-49 years, using data from GenomegaDB, a genetic database of Indians living in India. An in-house developed custom chip, having variants associated with various cancers, cardiovascular, neurological, gastro-intestinal, metabolic and auto-immune disorders, was used to generate genotype data. Logistic regression analysis with top five genetic principal components as covariates resulted in 11 variants to be significantly associated with longevity at a p-value threshold of 5×10 −4 . Alleles associated with slower heart rate (rs365990, MYH6), lower risk of osteoporosis and short body height (rs2982570, ESR1), decreased risk of schizophrenia (rs1339227, RIMS1-KCNQ5) and decreased risk of anxiety and neuroticism (rs391957, HSPA5) were found to have higher frequency in LLIs. Alleles associated with increased risk of atrial fibrillation (rs3903239, GORAB-PRRX1) and biliary disorders (rs2002042, ABCC2) were found have lower frequency. The G allele of rs2802292 from FOXO3A gene, associated with longevity in Japanese, German and French centenarians, was also found to be significant in this population (P=0.027). Pathway enrichment analysis revealed that the genes involved in oxidative stress, apoptosis, DNA damage repair, glucose metabolism and energy metabolism were significantly involved in increasing the longevity. Results of our study demonstrate the genetic basis of healthy aging and longevity in the population.