Jennifer A Smith1,2, Wei Zhao1, Miao Yu1, Kalee E Rumfelt1, Priya Moorjani3,4, Andrea Ganna5, Aparajit B Dey6, Jinkook Lee7, Sharon L R Kardia1. 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, California, USA. 4. Center for Computational Biology, University of California, Berkeley, California, USA. 5. Institute for Molecular Medicine Finland, Helsinki, Finland. 6. Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India. 7. Department of Economics, University of Southern California, Los Angeles, California, USA.
Abstract
BACKGROUND/ OBJECTIVES: Genetic factors play an important role in Alzheimer's disease (AD) and cognitive aging. However, it is unclear whether risk loci identified in European ancestry (EA) populations have similar effects in other groups, such as South Asians. DESIGN: We investigated the allelic distribution and cognitive associations of 56 known AD risk single-nucleotide polymorphisms (SNPs) identified from three EA genome-wide association studies (EA-GWASs) in a South Asian population. Single SNP and genetic risk score (GRS) associations with measures of episodic memory were assessed. SETTING: The Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). PARTICIPANTS: A total of 906 LASI-DAD participants from diverse states in India. MEASUREMENTS: Participants were genotyped using the Illumina Global Screening Array and imputed with 1000G Phase 3v5. Cognitive measures included total learning and delayed word recall. RESULTS: Although only a few SNPs were significantly associated with memory scores (P < .05), effect estimates from the EA-GWAS and the LASI-DAD showed moderate correlation (0.35-0.88) in the expected direction. GRSs were also associated with memory scores, although percentage variation explained was small (0.1%-0.6%). CONCLUSIONS: Discrepancies in allele frequencies and cognitive association results suggest that genetic factors found predominantly through EA-GWASs may play a limited role in South Asians. However, the extent of differences in the genetic architecture of AD and cognition in EA and South Asians remains uncertain. There is also a critical need to perform a more comprehensive assessment of the mutational spectrum of South Asia to identify novel genetic variants associated with AD and cognition in this population. J Am Geriatr Soc 68:S45-S53, 2020.
BACKGROUND/ OBJECTIVES: Genetic factors play an important role in Alzheimer's disease (AD) and cognitive aging. However, it is unclear whether risk loci identified in European ancestry (EA) populations have similar effects in other groups, such as South Asians. DESIGN: We investigated the allelic distribution and cognitive associations of 56 known AD risk single-nucleotide polymorphisms (SNPs) identified from three EA genome-wide association studies (EA-GWASs) in a South Asian population. Single SNP and genetic risk score (GRS) associations with measures of episodic memory were assessed. SETTING: The Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). PARTICIPANTS: A total of 906 LASI-DAD participants from diverse states in India. MEASUREMENTS: Participants were genotyped using the Illumina Global Screening Array and imputed with 1000G Phase 3v5. Cognitive measures included total learning and delayed word recall. RESULTS: Although only a few SNPs were significantly associated with memory scores (P < .05), effect estimates from the EA-GWAS and the LASI-DAD showed moderate correlation (0.35-0.88) in the expected direction. GRSs were also associated with memory scores, although percentage variation explained was small (0.1%-0.6%). CONCLUSIONS: Discrepancies in allele frequencies and cognitive association results suggest that genetic factors found predominantly through EA-GWASs may play a limited role in South Asians. However, the extent of differences in the genetic architecture of AD and cognition in EA and South Asians remains uncertain. There is also a critical need to perform a more comprehensive assessment of the mutational spectrum of South Asia to identify novel genetic variants associated with AD and cognition in this population. J Am Geriatr Soc 68:S45-S53, 2020.
Authors: Bei Jun Chen; James D Mills; Konii Takenaka; Nicola Bliim; Glenda M Halliday; Michael Janitz Journal: J Neurochem Date: 2016-09-05 Impact factor: 5.372
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