AFA: Ancestry-specific allele frequency estimation in admixed populations: The Hispanic Community Health Study/Study of Latinos
Year: 2022
Type: article
Abstract: Allele frequency estimates in admixed populations, such as Hispanics and Latinos, rely on the sample’s specific admixture composition and thus may differ between two seemingly similar populations. However, ancestry-specific allele frequencies, i.e., pertaining to the ancestral populations of an admixed group, may be particularly useful for prioritizing genetic variants for genetic discovery and personalized genomic health. We developed a method, ancestry-specific allele frequency estimation in admixed populations (AFA), to estimate the frequencies of biallelic variants in admixed populations with an unlimited number of ancestries. AFA uses maximum-likelihood estimation by modeling the conditional probability of having an allele given proportions of genetic ancestries. It can be applied using either local ancestry interval proportions encompassing the variant (local-ancestry-specific allele frequency estimations in admixed populations [LAFAs]) or global proportions of genetic ancestries (global-ancestry-specific allele frequency estimations in admixed populations [GAFAs]), which are easier to compute and are more widely available. Simulations and comparisons to existing software demonstrated the high accuracy of the method. We implemented AFA on high-quality imputed data of ∼9,000 Hispanics and Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an understudied, admixed population with three predominant continental ancestries: Amerindian, European, and African. Comparison of the European and African estimated frequencies to the respective gnomAD frequencies demonstrated high correlations (Pearson R2 = 0.97–0.99). We provide a genome-wide dataset of the estimated ancestry-specific allele frequencies for available variants with allele frequency between 5% and 95% in at least one of the three ancestral populations. Association analysis of Amerindian-enriched variants with cardiometabolic traits identified five loci associated with lipid traits in Hispanics and Latinos, demonstrating the utility of ancestry-specific allele frequencies in admixed populations.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,300
Funders: Office of Dietary Supplements, University of Miami, Northwestern University, San Diego State University, University of Michigan, University of Washington, National Institutes of Health, University of Illinois at Urbana-Champaign, Albert Einstein College of Medicine, Yeshiva University, Gillings School of Public Health, University of Illinois at Chicago, 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: The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data Commons, G1052645489, G1081972346, G1086382119, G1121130830, G1140476625, G122677224, G1312369436, G1327559120, Hispanic Community Health Study, G1455175283, G1666450717, Local ancestry inference for complex admixtures, G1818487580, G1866572497, G1888983140, G1984718218, G2087483592, G2096685756, G2128161193, Rare variants and NHLBI traits in deeply phenotyped cohorts, G232264632, G2466919156, HISPANIC COMMUNITY HEALTH STUDY - FIELD CENTER, G2528054427, G2644289446, G2651066328, G2655143993, Using Genetic and Blood Metabolites to Understand the Risk of Alzheimer's Disease in Latinos, G2970637568, G3078883119, G308844681, G3256118428, G3332710595, Hispanic Community Health Study, G3614733703, G3667269547, G3808803955, G3811607389, G3850122098, G3921432814, Rare variants and NHLBI traits in deeply phenotyped cohorts, G432753757, Hispanic Community Health Study, G4497211205, G4592244384, G5108924296, G5129651400, G5163278296, G5223154479, G528357465, G5298149031, G5365244667, G5397198720, HISPANIC COMMUNITY HEALTH STUDY - COORDINATING CENTER, G543802643, G5496802768, G5785169696, G5818672366, The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data Commons, NHLBI Data Stage Coordinating Center, G5935820280, G596642789, G5988662542, G5993399974, G6075306088, G6149955053, G6170501256, G6202424770, G627395113, G631129105, G6615318374, G7132511053, The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data Commons, G7519571385, G7667010295, The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data Commons, G820454163, G8222448866, G8328619368, Studies of Rare Genetic Variation in the Isolated Population of Sardinia, G8532757437, G8987601928, G9000180696, G937084196, G940445018, G954279374
OpenAlex ID: W4213412458