Detection and characterization of male sex chromosome abnormalities in the UK Biobank study.

Autor:	Zhao Y; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom., Gardner EJ; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom., Tuke MA; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Zhang H; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Pietzner M; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom; Computational Medicine, Berlin Institute of Health (BIH) at Charité, Universitätsmedizin Berlin, Berlin, Germany., Koprulu M; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom., Jia RY; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom., Ruth KS; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Wood AR; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Beaumont RN; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Tyrrell J; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Jones SE; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland., Lango Allen H; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom., Day FR; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom., Langenberg C; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom; Computational Medicine, Berlin Institute of Health (BIH) at Charité, Universitätsmedizin Berlin, Berlin, Germany., Frayling TM; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Weedon MN; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom., Perry JRB; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom., Ong KK; MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom. Electronic address: Ken.Ong@mrc-epid.cam.ac.uk., Murray A; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom. Electronic address: A.Murray@exeter.ac.uk.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2022 Sep; Vol. 24 (9), pp. 1909-1919. Date of Electronic Publication: 2022 Jun 09.
DOI:	10.1016/j.gim.2022.05.011
Abstrakt:	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. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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