biostudies-literatureHawkes GInnovative Medicines InitiativeNIEHS NIH HHSNHLBI NIH HHSMedical Research CouncilNCI NIH HHSNNF Center for Basic Metabolic ResearchInnovative Medicines Initiative (IMI)Wellcome TrustNovo Nordisk FondenBiotechnology and Biological Sciences Research Council8549https://www.ebi.ac.uk/biostudies/studies/S-EPMC11450065biostudies-literatureUnknown15(1)The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P <  6×10-10 after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based Nature communicationsWhole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.PMC11450065NNF20OC0059313CBMR - 008R35 CA197449R01 HL163560MR/M008924/1BB/K003240/1P30 ES010126R01 HL105756WT101650MA875534Psaty BMKardia SLRChami NDarbar DGuo XLocke JMBoerwinkle ELin XManning AMandla RChung MKMurray ACurran JEWood ARWright CFFrayling TMTelen MJPatel KHe JEllinor PTAlbert CMJustice AERedline SLi XLi ZShoemaker MBLiu CTBrody JAHawkes GHwu CMFornage MKalyani RRYanek LRAshley-Koch AEGordeuk VRMurabito JMBeaumont RNNaseri TSilverman EKLoos RJFOwens NViali SMinster RLWeiss STArnett DKLubitz SAZhou HKaplan RAshrani AAPalmer NDWeedon MNKooperberg CNHLBI Trans-Omics for Precision Medicine (TOPMed) ConsortiumBarnes KCChen YICarson APMitchell BDNorth KEfalseWhole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P <  6×10-10 after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based 2024-01-01T00:00:00Z2024 Oct2026-04-30T00:08:23.657Z2025-04-06T12:49:50.79ZS-EPMC114500653936288010.1038/s41467-024-52579-w