PDF(Pubmed)
Abstract：
OBJECTIVE: The association of water loading with several infections remains unclear. Observational studies are hard to investigate definitively due to potential confounders. In this study, we employed Mendelian randomization (MR) analysis to assess the association between genetically predicted whole body water mass (BWM) and several infections.
METHODS: BWM levels were predicted among 331,315 Europeans in UK Biobank using 418 SNPs associated with BWM. For outcomes, we used genome-wide association data from the UK Biobank and FinnGen consortium, including sepsis, pneumonia, intestinal infections, urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inverse-variance weighted MR analyses as well as a series of sensitivity analyses were conducted.
RESULTS: Genetic prediction of BWM is associated with an increased risk of sepsis (OR 1.34; 95% CI 1.19 to 1.51; P = 1.57 × 10- 6), pneumonia (OR: 1.17; 95% CI 1.08 to 1.29; P = 3.53 × 10- 4), UTIs (OR: 1.26; 95% CI 1.16 to 1.37; P = 6.29 × 10- 8), and SSTIs (OR: 1.57; 95% CI 1.25 to 1.96; P = 7.35 × 10- 5). In the sepsis and pneumonia subgroup analyses, the relationship between BWM and infection was observed in bacterial but not in viral infections. Suggestive evidence suggests that BWM has an effect on viral intestinal infections (OR: 0.86; 95% CI 0.75 to 0.99; P = 0.03). There is limited evidence of an association between BWM levels and bacteria intestinal infections, and genitourinary tract infection (GUI) in pregnancy. In addition, MR analyses supported the risk of BWM for several edematous diseases. However, multivariable MR analysis shows that the associations of BWM with sepsis, pneumonia, UTIs and SSTIs remains unaffected when accounting for these traits.
CONCLUSIONS: In this study, the causal relationship between BWM and infectious diseases was systematically investigated. Further prospective studies are necessary to validate these findings.
METHODS: BWM levels were predicted among 331,315 Europeans in UK Biobank using 418 SNPs associated with BWM. For outcomes, we used genome-wide association data from the UK Biobank and FinnGen consortium, including sepsis, pneumonia, intestinal infections, urinary tract infections (UTIs) and skin and soft tissue infections (SSTIs). Inverse-variance weighted MR analyses as well as a series of sensitivity analyses were conducted.
RESULTS: Genetic prediction of BWM is associated with an increased risk of sepsis (OR 1.34; 95% CI 1.19 to 1.51; P = 1.57 × 10- 6), pneumonia (OR: 1.17; 95% CI 1.08 to 1.29; P = 3.53 × 10- 4), UTIs (OR: 1.26; 95% CI 1.16 to 1.37; P = 6.29 × 10- 8), and SSTIs (OR: 1.57; 95% CI 1.25 to 1.96; P = 7.35 × 10- 5). In the sepsis and pneumonia subgroup analyses, the relationship between BWM and infection was observed in bacterial but not in viral infections. Suggestive evidence suggests that BWM has an effect on viral intestinal infections (OR: 0.86; 95% CI 0.75 to 0.99; P = 0.03). There is limited evidence of an association between BWM levels and bacteria intestinal infections, and genitourinary tract infection (GUI) in pregnancy. In addition, MR analyses supported the risk of BWM for several edematous diseases. However, multivariable MR analysis shows that the associations of BWM with sepsis, pneumonia, UTIs and SSTIs remains unaffected when accounting for these traits.
CONCLUSIONS: In this study, the causal relationship between BWM and infectious diseases was systematically investigated. Further prospective studies are necessary to validate these findings.
摘要：
目的：水负荷与几种感染的关系尚不清楚。由于潜在的混杂因素，观察性研究很难进行明确的调查。在这项研究中,我们采用孟德尔随机化(MR)分析来评估基因预测的全身水质量(BWM)与几种感染之间的关联.
方法：使用与BWM相关的418个SNP，在英国生物库的331,315个欧洲人中预测了BWM水平。对于结果，我们使用了英国生物银行和FinnGen联盟的全基因组关联数据，包括败血症,肺炎,肠道感染,尿路感染（UTI）和皮肤和软组织感染（STTI）。进行了逆方差加权MR分析以及一系列敏感性分析。
结果：BWM的遗传预测与脓毒症风险增加相关（OR1.34；95％CI1.19至1.51；P=1.57×10-6），肺炎（OR：1.17；95%CI1.08至1.29；P=3.53×10-4），尿路感染（OR：1.26；95%CI1.16至1.37；P=6.29×10-8），和SSTIs（OR：1.57；95%CI1.25至1.96；P=7.35×10-5）。在脓毒症和肺炎亚组分析中，在细菌感染中观察到BWM与感染之间的关系，而在病毒感染中未观察到。证据表明，BWM对病毒性肠道感染有影响（OR：0.86；95％CI0.75至0.99；P=0.03）。有有限的证据表明BWM水平和细菌肠道感染之间的关联，和妊娠期泌尿生殖道感染（GUI）。此外,MR分析支持了几种水肿性疾病的BWM风险。然而,多变量MR分析表明，BWM与脓毒症，肺炎,考虑到这些性状时，UTI和STTI不受影响。
结论：在这项研究中，系统研究了BWM与传染病的因果关系。需要进一步的前瞻性研究来验证这些发现。
方法：使用与BWM相关的418个SNP，在英国生物库的331,315个欧洲人中预测了BWM水平。对于结果，我们使用了英国生物银行和FinnGen联盟的全基因组关联数据，包括败血症,肺炎,肠道感染,尿路感染（UTI）和皮肤和软组织感染（STTI）。进行了逆方差加权MR分析以及一系列敏感性分析。
结果：BWM的遗传预测与脓毒症风险增加相关（OR1.34；95％CI1.19至1.51；P=1.57×10-6），肺炎（OR：1.17；95%CI1.08至1.29；P=3.53×10-4），尿路感染（OR：1.26；95%CI1.16至1.37；P=6.29×10-8），和SSTIs（OR：1.57；95%CI1.25至1.96；P=7.35×10-5）。在脓毒症和肺炎亚组分析中，在细菌感染中观察到BWM与感染之间的关系，而在病毒感染中未观察到。证据表明，BWM对病毒性肠道感染有影响（OR：0.86；95％CI0.75至0.99；P=0.03）。有有限的证据表明BWM水平和细菌肠道感染之间的关联，和妊娠期泌尿生殖道感染（GUI）。此外,MR分析支持了几种水肿性疾病的BWM风险。然而,多变量MR分析表明，BWM与脓毒症，肺炎,考虑到这些性状时，UTI和STTI不受影响。
结论：在这项研究中，系统研究了BWM与传染病的因果关系。需要进一步的前瞻性研究来验证这些发现。
