biostudies-literatureElgart MNHLBI NIH HHS100844https://www.ebi.ac.uk/biostudies/studies/S-EPMC9797952biostudies-literatureUnknown3(12)We develop a closed-form Haseman-Elston estimator for genetic and environmental correlation coefficients between complex phenotypes, which we term HEc, that is as precise as GCTA yet ∼20× faster. We estimate genetic and environmental correlations between over 7,000 phenotype pairs in subgroups from the Trans-Omics in Precision Medicine (TOPMed) program. We demonstrate substantial differences in both heritabilities and genetic correlations for multiple phenotypes and phenotype pairs between individuals of self-reported Black, Hispanic/Latino, and White backgrounds. We similarly observe differences in many of the genetic and environmental correlations between genders. To estimate the contribution of genetics to the observed phenotypic correlation, we introduce "fractional genetic correlationCell reports. MedicineCorrelations between complex human phenotypes vary by genetic background, gender, and environment.PMC9797952R21 HL145425Goodman MOIsasi CHeard-Costa NLPsaty BMRotter JIVasan RSGuo XFranceschini NCorrea ARich SSChen HMorrison ACXu HHernandez RRedline STrans-Omics for Precision Medicine (TOPMed) ConsortiumElgart MSofer TManichaikul AWLloyd-Jones DMFornage Mde Vries PSKaplan RCfalseCorrelations between complex human phenotypes vary by genetic background, gender, and environment.We develop a closed-form Haseman-Elston estimator for genetic and environmental correlation coefficients between complex phenotypes, which we term HEc, that is as precise as GCTA yet ∼20× faster. We estimate genetic and environmental correlations between over 7,000 phenotype pairs in subgroups from the Trans-Omics in Precision Medicine (TOPMed) program. We demonstrate substantial differences in both heritabilities and genetic correlations for multiple phenotypes and phenotype pairs between individuals of self-reported Black, Hispanic/Latino, and White backgrounds. We similarly observe differences in many of the genetic and environmental correlations between genders. To estimate the contribution of genetics to the observed phenotypic correlation, we introduce "fractional genetic correlation2022-01-01T00:00:00Z2022 Dec2025-04-19T14:53:37.421Z2025-04-19T14:53:37.421ZS-EPMC97979523651307310.1016/j.xcrm.2022.100844