A genome-wide association study of susceptibility to upper urinary tract infections

Helene M Flatby; Anuradha Ravi; Kristin V Liyanarachi; Jan E Afset; Humaira Rasheed; Ben M Brumpton; Kristian Hveem; Bjørn O Åsvold; Andrew T DeWan; Erik Solligård; Jan K Damås; Tormod Rogne

doi:10.1093/infdis/jiae231

A genome-wide association study of susceptibility to upper urinary tract infections

J Infect Dis. 2024 May 7:jiae231. doi: 10.1093/infdis/jiae231. Online ahead of print.

Authors

Helene M Flatby^{1

2}, Anuradha Ravi^{1

3}, Kristin V Liyanarachi^{1

4}, Jan E Afset^{1

5

6}, Humaira Rasheed^{7

8}, Ben M Brumpton^{7

8

9}, Kristian Hveem^{7

10}, Bjørn O Åsvold^{11

9

7}, Andrew T DeWan^{12

1}, Erik Solligård^{1

13}, Jan K Damås^{1

14

4}, Tormod Rogne^{12

1}

Affiliations

¹ Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
² Clinic of Anaesthesia and Intensive Care, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
³ Department of Medical Genetics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
⁴ Department of Infectious Diseases, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
⁵ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁶ Department of Medical Microbiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
⁷ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
⁸ Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
⁹ HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
¹⁰ Department of Research, Innovation, and Education, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
¹¹ Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
¹² Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA.
¹³ Helse Møre og Romsdal Hospital Trust, Ålesund, Norway.
¹⁴ Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

PMID: 38713594
DOI: 10.1093/infdis/jiae231

Abstract

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.

Keywords: Genome-wide association study; Mendelian randomization; Pyelonephritis; Smoking; Upper urinary tract infection.