{"doi":"10.1093/hmg/ddab130","title":"OUP accepted manuscript","abstract":"It is important to study the genetics of complex traits in diverse populations. Here, we introduce covariate-adjusted linkage disequilibrium (LD) score regression (cov-LDSC), a method to estimate SNP-heritability (${\\boldsymbol{h}}_{\\boldsymbol{g}}^{\\mathbf{2}})$ and its enrichment in homogenous and admixed populations with summary statistics and in-sample LD estimates. In-sample LD can be estimated from a subset of the genome-wide association studies samples, allowing our method to be applied efficiently to very large cohorts. In simulations, we show that unadjusted LDSC underestimates ${\\boldsymbol{h}}_{\\boldsymbol{g}}^{\\mathbf{2}}$ by 10-60% in admixed populations; in contrast, cov-LDSC is robustly accurate. We apply cov-LDSC to genotyping data from 8124 individuals, mostly of admixed ancestry, from the Slim Initiative in Genomic Medicine for the Americas study, and to approximately 161 000 Latino-ancestry individuals, 47 000 African American-ancestry individuals and 135 000 European-ancestry individuals, as classified by 23andMe. We estimate ${\\boldsymbol{h}}_{\\boldsymbol{g}}^{\\mathbf{2}}$ and detect heritability enrichment in three quantitative and five dichotomous phenotypes, making this, to our knowledge, the most comprehensive heritability-based analysis of admixed individuals to date. Most traits have high concordance of ${\\boldsymbol{h}}_{\\boldsymbol{g}}^{\\mathbf{2}}$ and consistent tissue-specific heritability enrichment among different populations. However, for age at menarche, we observe population-specific heritability estimates of ${\\boldsymbol{h}}_{\\boldsymbol{g}}^{\\mathbf{2}}$. We observe consistent patterns of tissue-specific heritability enrichment across populations; for example, in the limbic system for BMI, the per-standardized-annotation effect size $ \\tau $* is 0.16 ± 0.04, 0.28 ± 0.11 and 0.18 ± 0.03 in the Latino-, African American- and European-ancestry populations, respectively. Our approach is a powerful way to analyze genetic data for complex traits from admixed populations.","journal":"Human Molecular Genetics","year":2021,"id":161828,"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":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":624121,"name":"Xinyi Li","orcid":"0000-0002-0221-0525","position":1,"is_corresponding":false},{"id":292332,"name":"Xin Wang","orcid":"0000-0001-7242-357X","position":2,"is_corresponding":false},{"id":95472,"name":"Steven Gazal","orcid":"0000-0003-4510-5730","position":3,"is_corresponding":false},{"id":253982,"name":"Josep M. Mercader","orcid":"0000-0001-8494-3660","position":4,"is_corresponding":false},{"id":677769,"name":"Benjamin M Neale","orcid":null,"position":5,"is_corresponding":false},{"id":677770,"name":"Jose C Florez","orcid":null,"position":6,"is_corresponding":false},{"id":228679,"name":"Adam Auton","orcid":"0000-0002-1630-1225","position":7,"is_corresponding":false},{"id":22002,"name":"Alkes L. Price","orcid":"0000-0002-2971-7975","position":8,"is_corresponding":false},{"id":347763,"name":"Yang Luo","orcid":"0000-0001-9355-603X","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T23:44:56.409311Z","pmid":"33987664","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":[]}