Polygenic risk score for general cognitive function is associated with measures of cognition in South Asians from the LASI-DAD Study.

Abstract

Genome wide association studies (GWAS) conducted primarily in European Ancestry (EA) have identified hundreds of single nucleotide polymorphisms (SNPs) that are associated with general cognitive function. The association between these SNPs and cognitive function has not yet been evaluated in South Asians yet, either individually or in polygenic risk scores (PRS) which aggregate the effects from many SNPs across the genome. The goal of this study was to investigate whether SNPs identified in EA GWAS, either individually or as a PRS, were associated with a general cognitive factor and the Hindi version of the Mini-Mental State Examination (HMSE) score in 932 South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD). Participants were genotyped using the Illumina Global Screening Array and imputed to 1000G Phase 3v5. We used linear models to assess the association between 130 top SNPs from the EA GWAS (p<5e-08) and both measures of cognitive function after controlling for age, gender, and population structure. We also evaluated the association between PRSs using the top GWAS SNPs and the cognitive measures using the same models. Finally, we estimated the variation in cognitive function explained by the cognitive function PRS, Alzheimer's disease (AD) PRSs, and/or APOE e2 and e4 genotypes individually or simultaneously. Preliminary analyses showed that none of the GWAS SNPs were significantly associated either of the cognitive measures after multiple testing correction. The PRS, however, was significantly associated with the general cognitive factor and HMSE score (p<0.025). The PRS explained 0.40% and 0.59% of the variance in the general cognitive factor and HMSE score, and explained 1.50% and 1.85% of the variance when coupled with AD PRSs and APOE genotypes. SNPs identified for cognitive function in EA GWAS may not be as strongly associated in South Asians. However, the genetic risk score for both general cognitive function and AD contribute additively to cognitive function in LASI-DAD participants. Future large scale GWAS of general cognitive function and AD are needed to identify specific risk variants for cognition in South Asians.