Indian‐enriched genetic variants are associated with cognitive function

INTRODUCTION: Little is known about genetic risk factors for dementia in South Asians. Examining genetic variants that occur at higher frequency in India compared to other ancestries (i.e., Indian enriched variants) may identify genetic associations with cognitive function that are potentially unique to the Indian population. METHODS: We examined whether 3.43 million variants enriched in India compared to European (EA), East Asian (EAS), and African (AFR) ancestries were associated with seven measures of cognitive function in 2680 older adults from the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). RESULTS: Identified Indian-enriched variants were largely near loci previously associated with neuropsychiatric traits, N-acetyltaurine levels, educational attainment, and cardiovascular risk factors for dementia. Several variants near genes previously associated with intellectual disabilities and synaptic function exhibited sex-specific effects. DISCUSSION: Indian-enriched variants may play a significant role in cognitive function in South Asians living in India. HIGHLIGHTS: Some cognitive function-associated variants are unique to, or more common in, India. Implicated genes were in cardiovascular, neurocognitive, and inflammatory pathways. Some Indian-enriched genetic variants demonstrate sex-specific effects.