| Title: | Detection and characterization of male sex chromosome abnormalities in the UK Biobank study |
| Journal: | Genetics in Medicine |
| Published: | 9 Jun 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35687092/ |
| DOI: | https://doi.org/10.1016/j.gim.2022.05.011 |
| URL: | http://www.gimjournal.org/article/S1098360022007778/pdf |
Publication 14012
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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.</p>
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.</p>
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).</p>
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.</p>
8 Keywords
- Biological Specimen Banks
- Diabetes Mellitus, Type 2
- Humans
- Klinefelter Syndrome
- Male
- Sex Chromosome Aberrations
- United Kingdom
- XYY Karyotype
20 Authors
- Yajie Zhao
- Eugene J Gardner
- Marcus A Tuke
- Huairen Zhang
- Maik Pietzner
- Mine Koprulu
- Raina Y Jia
- Katherine S Ruth
- Andrew R Wood
- Robin N Beaumont
- Jessica Tyrrell
- Samuel E Jones
- Hana Lango Allen
- Felix R Day
- Claudia Langenberg
- Timothy M Frayling
- Michael N Weedon
- John R B Perry
- Ken K Ong
- Anna Murray
1 Application
| Application ID | Title |
|---|---|
| 9905 | Using genetics to elucidate the relationship between socioeconomic/behavioural traits and disease |
Enabling scientific discoveries that improve human health