Research Institute of the Hospital for Sick Children, Toronto, Ontario, Canada.
Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.
Int J Obes (Lond). 2022 Jan;46(1):235-237. doi: 10.1038/s41366-021-00960-w. Epub 2021 Sep 3.
The genetic architecture of testosterone is highly distinct between sexes. Moreover, obesity is associated with higher testosterone in females but lower testosterone in males. Here, we ask whether male-specific testosterone variants are associated with a male pattern of obesity and type 2 diabetes (T2D) in females, and vice versa. In the UK Biobank, we conducted sex-specific genome-wide association studies and computed polygenic scores for total (PGS) and bioavailable testosterone (PGS). We tested sex-congruent and sex-incongruent associations between sex-specific PGSs and metabolic traits, as well as T2D diagnosis. Female-specific PGS was associated with an elevated cardiometabolic risk and probability of T2D, in both sexes. Male-specific PGS was associated with traits conferring a lower cardiometabolic risk and probability of T2D, in both sexes. We demonstrate the value in considering polygenic testosterone as sex-related continuous traits, in each sex.
睾酮的遗传结构在性别之间有很大的差异。此外，肥胖与女性体内的睾酮水平升高有关，而与男性体内的睾酮水平降低有关。在这里，我们想知道男性特有的睾酮变体是否与女性的肥胖和 2 型糖尿病（T2D）男性模式有关，反之亦然。在英国生物银行中，我们进行了性别特异性全基因组关联研究，并计算了总（PGS）和生物可利用睾酮（PGS）的多基因评分。我们测试了性别一致和性别不一致的性别特异性 PGS 与代谢特征以及 T2D 诊断之间的关联。女性特异性 PGS 与心血管代谢风险升高和 T2D 的发生几率相关，而不论性别如何。男性特异性 PGS 与降低心血管代谢风险和 T2D 发生几率的特征相关，而不论性别如何。我们证明了将多基因睾酮作为与性别相关的连续特征来考虑的价值，无论在哪个性别中。
