Background Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs). Methods We used data from UK Biobank, The Trøndelag Health Study (HUNT), and Michigan Genomics Initiative (MGI) to conduct genome-wide association studies (GWASs) and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs. Results One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for the females, SCAMP1−AS1 for the males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (OR of 4.84, P = 4.50E-06 and OR of 2.79, P = 3.02E-05, respectively). Conclusions We found that genetic variants near TSN was associated with the risk of upper UTIs among females. In addition, we found several genetic loci with suggestive associations with the risk of upper UTIs. Finally, MR analyses found smoking to be a potential causal risk factor for upper UTIs.

中文翻译：

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上尿路感染易感性的全基因组关联研究

背景我们的目标是确定上尿路感染（UTI）的遗传和可改变的危险因素。方法 我们使用来自英国生物银行、特伦德拉格健康研究 (HUNT) 和密歇根基因组计划 (MGI) 的数据对上尿路感染进行全基因组关联研究 (GWAS) 和性别分层分析。进行孟德尔随机化 (MR) 分析来检查心脏代谢危险因素与上尿路感染之间的潜在因果关系。结果 一个全基因组显着（P ≤ 5E-08）位点与上尿路感染的易感性相关，在仅限女性的分析中，该位点位于 TSN 附近。此外，我们还确定了女性 DNAI3 附近、男性 SCAMP1−AS1 附近以及两性 TSN、LINC00603 和 HLA-DQA2 附近的暗示性 (P ≤ 5E-06) 位点。在 MR 分析中，较高的基因预测终生吸烟评分与女性和男女患上尿路感染的风险增加相关（OR 分别为 4.84，P = 4.50E-06 和 OR 2.79，P = 3.02E-05） 。结论 我们发现 TSN 附近的遗传变异与女性上尿路感染的风险相关。此外，我们还发现了几个与上尿路感染风险相关的基因位点。最后，MR 分析发现吸烟是上尿路感染的潜在危险因素。