{"doi":"10.17615/0ety-ss26","title":"A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos","abstract":"Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%–54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10−10, minor allele frequency ≥ 1%, proportion of variance explained [PEV] mean = 3.4%, PEVrange = 1%–22%) with generalized effects in two population-based studies and confirmed 301 known locus-metabolite associations. Half of the identified variants with generalized effect were located in genes, including five nonsynonymous variants. We identified co-localization with the expression quantitative trait loci at 105 discovered and 151 known loci-metabolites sets. rs5855544, upstream of SLC51A, was associated with higher levels of three steroid sulfates and co-localized with expression levels of SLC51A in several tissues. Mendelian randomization (MR) analysis identified several metabolites associated with coronary heart disease (CHD) and type 2 diabetes. For example, two variants located in or near CYP4F2 (rs2108622 and rs79400241, respectively), involved in vitamin E metabolism, were associated with the levels of octadecanedioate and vitamin E metabolites (gamma-CEHC and gamma-CEHC glucuronide); MR analysis showed that genetically high levels of these metabolites were associated with lower odds of CHD. Our findings document the genetic architecture of circulating metabolites in an underrepresented Hispanic/Latino community, shedding light on disease etiology.","journal":"UNC Libraries","year":2024,"id":499115,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51216,"name":"Alanna C. Morrison","orcid":"0000-0001-6381-4296","position":1,"is_corresponding":false},{"id":431554,"name":"E. Boerwinkle","orcid":null,"position":2,"is_corresponding":false},{"id":256103,"name":"Megan L. Grove","orcid":"0000-0001-6764-2508","position":3,"is_corresponding":false},{"id":526168,"name":"Q. Qi","orcid":null,"position":4,"is_corresponding":false},{"id":1346189,"name":"Hu Chen","orcid":"0000-0002-5691-6259","position":5,"is_corresponding":false},{"id":753,"name":"Peilin Jia","orcid":"0000-0003-4523-4153","position":6,"is_corresponding":false},{"id":240595,"name":"Elena V. Feofanova","orcid":"0000-0003-1428-7199","position":7,"is_corresponding":false},{"id":526071,"name":"K.E. North","orcid":null,"position":8,"is_corresponding":false},{"id":981573,"name":"Yue Dai","orcid":"0000-0002-1773-5228","position":9,"is_corresponding":false},{"id":980420,"name":"C.C. Laurie","orcid":null,"position":10,"is_corresponding":false},{"id":835348,"name":"R.C. Kaplan","orcid":null,"position":11,"is_corresponding":false},{"id":590482,"name":"J. Cai","orcid":"0009-0001-9381-4067","position":12,"is_corresponding":false},{"id":601616,"name":"M. Daviglus","orcid":null,"position":13,"is_corresponding":false},{"id":538012,"name":"Bing Yu","orcid":"0000-0001-6605-6742","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:45.971055Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}