{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Hujoel MLA"],"funding":["NIEHS NIH HHS","NHLBI NIH HHS","NIMH NIH HHS","NHGRI NIH HHS","NIH HHS"],"pubmed_abstract":["Structural variants (SVs) comprise the largest genetic variants, altering from 50 base pairs to megabases of DNA. However, SVs have not been effectively ascertained in most genetic association studies, leaving a key gap in our understanding of human complex trait genetics. We ascertained protein-altering SVs from UK Biobank whole-exome sequencing data (<i>n</i>=468,570) using haplotype-informed methods capable of detecting sub-exonic SVs and variation within segmental duplications. Incorporating SVs into analyses of rare variants predicted to cause gene loss-of-function (pLoF) identified 100 associations of pLoF variants with 41 quantitative traits. A low-frequency partial deletion of <i>RGL3</i> exon 6 appeared to confer one of the strongest protective effects of gene LoF on hypertension "],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.06.07.544066"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10274781"],"repository":["biostudies-literature"],"pubmed_title":["Hidden protein-altering variants influence diverse human phenotypes."],"pmcid":["PMC10274781"],"funding_grant_id":["OT2 OD026548","OT2 OD025315","OT2 OD025337","OT2 OD026549","F31 HL154537","OT2 OD025277","OT2 OD025276","R56 HG006855","U24 OD023121","K25 HL150334","F32 HL160061","U24 OD023163","U2C OD023196","OT2 OD026555","OT2 OD026554","F31 MH124393","OT2 OD026557","OT2 OD026556","OT2 OD023205","OT2 OD023206","OT2 OD026551","OT2 OD026550","OT2 OD026553","OT2 OD026552","R01 HG006855","U24 OD023176","T32 HG002295","DP2 ES030554"],"pubmed_authors":["Kamitaki N","Loh PR","Hujoel MLA","McCarroll SA","Mukamel RE","Terao C","Barton AR","Handsaker RE","Sherman MA"],"additional_accession":[]},"is_claimable":false,"name":"Hidden protein-altering variants influence diverse human phenotypes.","description":"Structural variants (SVs) comprise the largest genetic variants, altering from 50 base pairs to megabases of DNA. However, SVs have not been effectively ascertained in most genetic association studies, leaving a key gap in our understanding of human complex trait genetics. We ascertained protein-altering SVs from UK Biobank whole-exome sequencing data (<i>n</i>=468,570) using haplotype-informed methods capable of detecting sub-exonic SVs and variation within segmental duplications. Incorporating SVs into analyses of rare variants predicted to cause gene loss-of-function (pLoF) identified 100 associations of pLoF variants with 41 quantitative traits. A low-frequency partial deletion of <i>RGL3</i> exon 6 appeared to confer one of the strongest protective effects of gene LoF on hypertension ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jun","modification":"2026-04-08T15:34:03.368Z","creation":"2025-04-06T17:40:15.243Z"},"accession":"S-EPMC10274781","cross_references":{"pubmed":["37333244"],"doi":["10.1101/2023.06.07.544066"]}}