biostudies-literatureKim DAmerican Heart AssociationEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD NIH HHSDivision of Cancer Epidemiology and GeneticsNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNational Heart, Lung, and Blood InstituteNHLBI NIH HHSNovo Nordisk Foundation Center for Basic Metabolic ResearchNHGRI NIH HHSNCI NIH HHSNational Human Genome Research Institute113https://www.ebi.ac.uk/biostudies/studies/S-EPMC12502452biostudies-literatureUnknown17(1)<h4>Background</h4>Obesity is thought to increase cardiovascular disease (CVD) risk partly through dyslipidemia. Yet, obesity's effects on dyslipidemia are not uniform. Understanding the shared genetic basis between obesity and lipid traits can provide insight into this heterogeneity and its implications for CVD risk.<h4>Methods</h4>We examined local genetic correlations between three lipid measures [high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG)] and body mass index (BMI) using genome-wide association study summary statistics from European ancestry UK Biobank participants. We identified genomic loci with opposing genetic effects on obesity and dyslipidemia risk (protective BMI-lipid loci) and those with concordant directions fGenome medicineGenetic underpinnings of the heterogeneous impact of obesity on lipid levels and cardiovascular disease.PMC12502452R01HD057194903805R01HL142302R01HG010297R01 HL142302NNF22OC0074128R01 DK122503R01 HG010297R01DK122503Intramural Research ProgramR01 HD057194Kim DGordon-Larsen PYoung KLBerndt SIRich SSGraff MLoos RJFHighland HMSpracklen CNDarst BFAvery CLLundin JBuchanan VLPeters UGuo BWang ZLange LHaiman CABuyske SLange EManson JEZhao CRaffield LMSmit RAJGignoux CRKilpelainen TOKooperberg CCai YFornage MMarouli EHysong MRNorth KEfalseGenetic underpinnings of the heterogeneous impact of obesity on lipid levels and cardiovascular disease.<h4>Background</h4>Obesity is thought to increase cardiovascular disease (CVD) risk partly through dyslipidemia. Yet, obesity's effects on dyslipidemia are not uniform. Understanding the shared genetic basis between obesity and lipid traits can provide insight into this heterogeneity and its implications for CVD risk.<h4>Methods</h4>We examined local genetic correlations between three lipid measures [high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG)] and body mass index (BMI) using genome-wide association study summary statistics from European ancestry UK Biobank participants. We identified genomic loci with opposing genetic effects on obesity and dyslipidemia risk (protective BMI-lipid loci) and those with concordant directions f2025-01-01T00:00:00Z2025 Oct2026-06-04T06:17:02.172Z2026-05-06T03:13:34.149ZS-EPMC125024524105379110.1186/s13073-025-01522-9