Polygenic Risk Scores for Alzheimer's Disease and General Cognitive Function Are Associated With Measures of Cognition in Older South Asians

Wei Zhao; Jennifer A Smith; Yi Zhe Wang; Manjusha Chintalapati; Farah Ammous; Miao Yu; Priya Moorjani; Andrea Ganna; Alden Gross; Sharmistha Dey; Joyita Benerjee; Prasun Chatterjee; Aparajit B Dey; Jinkook Lee; Sharon L R Kardia

doi:10.1093/gerona/glad057

Polygenic Risk Scores for Alzheimer's Disease and General Cognitive Function Are Associated With Measures of Cognition in Older South Asians

J Gerontol A Biol Sci Med Sci. 2023 May 11;78(5):743-752. doi: 10.1093/gerona/glad057.

Authors

Wei Zhao^{1

2}, Jennifer A Smith^{1

2}, Yi Zhe Wang¹, Manjusha Chintalapati^{3

4}, Farah Ammous¹, Miao Yu¹, Priya Moorjani^{3

4}, Andrea Ganna⁵, Alden Gross⁶, Sharmistha Dey⁷, Joyita Benerjee⁸, Prasun Chatterjee⁸, Aparajit B Dey⁸, Jinkook Lee⁹, Sharon L R Kardia¹

Affiliations

¹ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
² Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA.
³ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
⁴ Center for Computational Biology, University of California, Berkeley, Berkeley, California, USA.
⁵ Institute for Molecular Medicine Finland, Helsinki, Finland.
⁶ Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁷ Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
⁸ Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India.
⁹ Department of Economics, University of Southern California, Los Angeles, California, USA.

Abstract

Genome-wide association studies (GWAS) conducted in European ancestry (EA) have identified hundreds of single-nucleotide polymorphisms (SNPs) associated with general cognitive function and/or Alzheimer's disease (AD). The association between these SNPs and cognitive function has not been fully evaluated in populations with complex genetic substructure such as South Asians. This study investigated whether SNPs identified in EA GWAS, either individually or as polygenic risk scores (PRSs), were associated with general cognitive function and 5 broad cognitive domains in 932 South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). We found that SNPs identified from AD GWAS were more strongly associated with cognitive function in LASI-DAD than those from a GWAS of general cognitive function. PRSs for general cognitive function and AD explained up to 1.1% of the variability in LASI-DAD cognitive domain scores. Our study represents an important stepping stone toward better characterization of the genetic architecture of cognitive aging in the Indian/South Asian population and highlights the need for further research that may lead to the identification of new variants unique to this population.

Keywords: Dementia; Genetic risk score; India; Population structure; Single-nucleotide polymorphism.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Aged
Alzheimer Disease* / epidemiology
Alzheimer Disease* / genetics
Cognition
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide
Risk Factors
South Asian People

Abstract

Publication types

MeSH terms

Grants and funding