Detection and characterization of male sex chromosome abnormalities in the UK Biobank study
dc.contributor.author | Zhao, Y | |
dc.contributor.author | Gardner, EJ | |
dc.contributor.author | Tuke, MA | |
dc.contributor.author | Zhang, H | |
dc.contributor.author | Pietzner, M | |
dc.contributor.author | Koprulu, M | |
dc.contributor.author | Jia, RY | |
dc.contributor.author | Ruth, KS | |
dc.contributor.author | Wood, AR | |
dc.contributor.author | Beaumont, RN | |
dc.contributor.author | Tyrrell, J | |
dc.contributor.author | Jones, SE | |
dc.contributor.author | Lango Allen, H | |
dc.contributor.author | Day, FR | |
dc.contributor.author | Langenberg, C | |
dc.contributor.author | Frayling, TM | |
dc.contributor.author | Weedon, MN | |
dc.contributor.author | Perry, JRB | |
dc.contributor.author | Ong, KK | |
dc.contributor.author | Murray, A | |
dc.date.accessioned | 2022-07-04T08:16:39Z | |
dc.date.issued | 2022-06-09 | |
dc.date.updated | 2022-07-03T12:10:39Z | |
dc.description.abstract | PURPOSE: The study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes. METHODS: We analyzed genotyping array or exome sequence data in 207,067 men of European ancestry aged 40 to 70 years from the UK Biobank and related these to extensive routine health record data. RESULTS: Only 49 of 213 (23%) of men whom we identified with KS and only 1 of 143 (0.7%) with 47,XYY had a diagnosis of abnormal karyotype on their medical records or self-report. We observed expected associations for KS with reproductive dysfunction (late puberty: risk ratio [RR] = 2.7; childlessness: RR = 4.2; testosterone concentration: RR = -3.8 nmol/L, all P < 2 × 10-8), whereas XYY men appeared to have normal reproductive function. Despite this difference, we identified several higher disease risks shared across both KS and 47,XYY, including type 2 diabetes (RR = 3.0 and 2.6, respectively), venous thrombosis (RR = 6.4 and 7.4, respectively), pulmonary embolism (RR = 3.3 and 3.7, respectively), and chronic obstructive pulmonary disease (RR = 4.4 and 4.6, respectively) (all P < 7 × 10-6). CONCLUSION: KS and 47,XYY were mostly unrecognized but conferred substantially higher risks for metabolic, vascular, and respiratory diseases, which were only partially explained by higher levels of body mass index, deprivation, and smoking. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Gates Fellowship | en_GB |
dc.description.sponsorship | Academy of Medical Sciences | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | UK Department of Business, Energy and Industrial Strategy | en_GB |
dc.description.sponsorship | British Heart Foundation | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.description.sponsorship | Cancer Research UK | en_GB |
dc.format.extent | S1098-3600(22)00777-8- | |
dc.format.medium | Print-Electronic | |
dc.identifier.citation | Published online 9 June 2022 | en_GB |
dc.identifier.doi | https://doi.org/10.1016/j.gim.2022.05.011 | |
dc.identifier.grantnumber | MR/T00200X/1 | en_GB |
dc.identifier.grantnumber | MC_UU_00006/1 | en_GB |
dc.identifier.grantnumber | MC_UU_00006/2 | en_GB |
dc.identifier.grantnumber | SBF004∖1079 | en_GB |
dc.identifier.grantnumber | SBF006∖1134 | en_GB |
dc.identifier.grantnumber | C18281/A29019 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/130141 | |
dc.identifier | ORCID: 0000-0002-6174-6135 (Weedon, Michael N) | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier / American College of Medical Genetics and Genomics | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/35687092 | en_GB |
dc.relation.url | https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access | en_GB |
dc.rights | © Crown Copyright 2022. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | en_GB |
dc.subject | 47,XYY | en_GB |
dc.subject | Disorders of sexual development | en_GB |
dc.subject | Endocrinology | en_GB |
dc.subject | Klinefelter syndrome | en_GB |
dc.subject | Thrombosis | en_GB |
dc.subject | Type 2 diabetes | en_GB |
dc.title | Detection and characterization of male sex chromosome abnormalities in the UK Biobank study | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-07-04T08:16:39Z | |
dc.identifier.issn | 1098-3600 | |
exeter.place-of-publication | United States | |
dc.description | This is the final version. Available on open access from Elsevier via the DOI in this reocrd | en_GB |
dc.description | Data Availability: All data are available via the UK Biobank Access Management System https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access. | en_GB |
dc.identifier.eissn | 1530-0366 | |
dc.identifier.journal | Genetics in Medicine | en_GB |
dc.relation.ispartof | Genet Med | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2022-05-16 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2022-06-09 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-07-04T08:13:01Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2022-07-04T08:16:46Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © Crown Copyright 2022. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).