当前位置: X-MOL 学术Nat. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Using human genetics to understand the disease impacts of testosterone in men and women
Nature Medicine ( IF 82.9 ) Pub Date : 2020-02-10 , DOI: 10.1038/s41591-020-0751-5
Katherine S Ruth 1 , Felix R Day 2 , Jessica Tyrrell 1 , Deborah J Thompson 3 , Andrew R Wood 1 , Anubha Mahajan 4 , Robin N Beaumont 1 , Laura Wittemans 2, 4 , Susan Martin 1 , Alexander S Busch 2, 5, 6 , A Mesut Erzurumluoglu 2 , Benjamin Hollis 2 , Tracy A O'Mara 7 , , Mark I McCarthy 4, 8, 9, 10 , Claudia Langenberg 2 , Douglas F Easton 3 , Nicholas J Wareham 2 , Stephen Burgess 11, 12 , Anna Murray 1 , Ken K Ong 2, 13 , Timothy M Frayling 1 , John R B Perry 2
Affiliation  

Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate that the genetic determinants of testosterone levels are substantially different between sexes and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1 s.d. higher testosterone increases the risks of type 2 diabetes (odds ratio (OR) = 1.37 (95% confidence interval (95% CI): 1.22–1.53)) and polycystic ovary syndrome (OR = 1.51 (95% CI: 1.33–1.72)) in women, but reduces type 2 diabetes risk in men (OR = 0.86 (95% CI: 0.76–0.98)). We also show adverse effects of higher testosterone on breast and endometrial cancers in women and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses.



中文翻译:

使用人类遗传学了解睾丸激素对男性和女性的疾病影响

睾酮补充剂因其对性功能、骨骼健康和身体成分的影响而被广泛使用,但其对疾病结果的影响尚不清楚。为了更好地理解这一点,我们在 425,097 名英国生物银行研究参与者中确定了睾酮水平和相关性激素特征的遗传决定因素。使用 2,571 个全基因组显着关联,我们证明了睾酮水平的遗传决定因素在性别之间存在显着差异,并且遗传上较高的睾酮对女性的代谢疾病有害,但对男性有益。例如,基因决定的高 1 标准差的睾酮会增加 2 型糖尿病(比值比 (OR) = 1.37(95% 置信区间 (95% CI):1.22–1.53))和多囊卵巢综合征(OR = 1.51 ( 95% CI:1.33–1.72)) 在女性中,但会降低男性患 2 型糖尿病的风险 (OR = 0.86 (95% CI: 0.76–0.98))。我们还显示了较高的睾丸激素对女性乳腺癌和子宫内膜癌以及男性前列腺癌的不利影响。我们的研究结果提供了对睾酮对疾病影响的见解,并强调了性别特异性遗传分析的重要性。

更新日期:2020-02-10
down
wechat
bug