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


Journal

Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831

Informations de publication

Date de publication:
09 2022
Historique:
received: 31 01 2022
revised: 15 05 2022
accepted: 16 05 2022
pubmed: 11 6 2022
medline: 9 9 2022
entrez: 10 6 2022
Statut: ppublish

Résumé

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. 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. 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 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.

Identifiants

pubmed: 35687092
pii: S1098-3600(22)00777-8
doi: 10.1016/j.gim.2022.05.011
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1909-1919

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T00200X/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18281/A29019
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00006/2
Pays : United Kingdom

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of Interest The authors declare no conflicts of interest.

Auteurs

Yajie Zhao (Y)

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.

Eugene J Gardner (EJ)

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.

Marcus A Tuke (MA)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

Huairen Zhang (H)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

Maik 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.

Mine Koprulu (M)

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.

Raina Y Jia (RY)

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.

Katherine S Ruth (KS)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

Andrew R Wood (AR)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

Robin N Beaumont (RN)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

Jessica Tyrrell (J)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

Samuel E 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.

Hana Lango Allen (H)

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.

Felix R Day (FR)

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.

Claudia 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.

Timothy M Frayling (TM)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

Michael N Weedon (MN)

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon & Exeter Hospital, Exeter, United Kingdom.

John R B Perry (JRB)

MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, Cambridge University, Cambridge, United Kingdom.

Ken K 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.

Anna 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.

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