Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos
Year: 2020
Type: review
Study design: Observational Study
Abstract: Cognitive function such as reasoning, attention, memory, and language is strongly correlated with brain aging. Compared to non-Hispanic whites, Hispanics/Latinos have a higher risk of cognitive impairment and dementia. The genetic determinants of cognitive function have not been widely explored in this diverse and admixed population. We conducted a genome-wide association analysis of cognitive function in up to 7600 middle aged and older Hispanics/Latinos (mean = 55 years) from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Four cognitive measures were examined: the Brief Spanish English Verbal Learning Test (B-SEVLT), the Word Fluency Test (WFT), the Digit Symbol Substitution Test (DSST), the Six-Item Screener (SIS). Four novel loci were identified: one for B-SEVLT at 4p14, two for WFT at 3p14.1 and 6p21.32, and one for DSST at 10p13. These loci implicate genes highly expressed in brain and previously connected to neurological diseases (UBE2K, FRMD4B, the HLA gene complex). By applying tissue-specific gene expression prediction models to our genotype data, additional genes highly expressed in brain showed suggestive associations with cognitive measures possibly indicating novel biological mechanisms, including IFT122 in the hippocampus for SIS, SNX31 in the basal ganglia for B-SEVLT, RPS6KB2 in the frontal cortex for WFT, and CSPG5 in the hypothalamus for DSST. These findings provide new information about the genetic determinants of cognitive function in this unique population. In addition, we derived a measure of general cognitive function based on these cognitive tests and generated genome-wide association summary results, providing a resource to the research community for comparison, replication, and meta-analysis in future genetic studies in Hispanics/Latinos.
Source: Translational Psychiatry
Authors: Xueqiu Jian, Tamar Sofer, Wassim Tarraf, Jan Bressler, Jessica D. Faul, Wei Zhao, Scott M. Ratliff, Melissa Lamar, Lenore J. Launer, Cathy C. Laurie, Neil Schneiderman, David R. Weir, Clinton B. Wright, Kristine Yaffe, Donglin Zeng, Charles DeCarli, Thomas H. Mosley, Jennifer A. Smith, Hector M. González, Myriam Fornage
Institutions: The University of Texas at San Antonio Health Science Center, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, Brigham and Women's Hospital, Harvard University, Wayne State University, University of Michigan, Institute for Social Research, Rush University Medical Center, Rush University, National Institutes of Health, National Institute on Aging, University of Washington, University of Miami, National Institute of Neurological Disorders and Stroke, University of California, San Francisco, University of North Carolina at Chapel Hill, University of California, Davis, University of Mississippi Medical Center, University of California San Diego
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,290
Funders: U.S. Department of Health and Human Services, Office of Dietary Supplements, University of Miami, Northwestern University, San Diego State University, University of Washington, National Institutes of Health, University of Illinois at Urbana-Champaign, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Institute on Minority Health and Health Disparities
Awards: G1081972346, G1121130830, G122677224, G1312369436, G1327559120, G1349668216, Hispanic Community Health Study, G1455175283, Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), G1666450717, G1818487580, G1866572497, G1888983140, G1984718218, G2128161193, G213973861, G2466919156, HISPANIC COMMUNITY HEALTH STUDY - FIELD CENTER, G2528054427, G2644289446, G2651066328, G2655143993, G2874865971, G2970637568, G2972637382, Hispanic Community Health Study, G3614733703, G3667269547, G3722034730, ADSP Follow-up in Multi-Ethnic Cohorts via Endophenotypes, Omics & Model Systems, G4143790175, G432753757, Hispanic Community Health Study, G4592244384, G4642931300, G4727311221, G5015503974, G5102588038, G5129651400, G528357465, G5365244667, G5372897717, G5397198720, HISPANIC COMMUNITY HEALTH STUDY - COORDINATING CENTER, G543802643, G5785169696, G5935820280, G596642789, G6075306088, G6088185517, G6149955053, G6202424770, G627395113, G7132511053, G7667010295, G820454163, G8932431361, G8987601928, G9000199330, G937084196
OpenAlex ID: W3044740254