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

Genome-wide association study Mendelian randomization Pyelonephritis Smoking Upper urinary tract infection

Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
07 May 2024
Historique:
received: 18 09 2023
revised: 21 03 2024
accepted: 30 04 2024
medline: 7 5 2024
pubmed: 7 5 2024
entrez: 7 5 2024
Statut: aheadofprint

Résumé

Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs). 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. 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). 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.

Sections du résumé

BACKGROUND BACKGROUND
Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs).
METHODS 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 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 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.

Identifiants

DOI: 10.1093/infdis/jiae231 PMID: 38713594
pubmed: 38713594
pii: 7666590
doi: 10.1093/infdis/jiae231
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Auteurs

Helene M Flatby (HM)

Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Clinic of Anaesthesia and Intensive Care, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
ORCID: 0000-0002-5700-020X

Anuradha Ravi (A)

Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Medical Genetics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Kristin V Liyanarachi (KV)

Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Infectious Diseases, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Jan E Afset (JE)

Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Medical Microbiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Humaira Rasheed (H)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
ORCID: 0000-0002-3331-5864

Ben M Brumpton (BM)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.

Kristian Hveem (K)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Research, Innovation, and Education, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Bjørn O Åsvold (BO)

Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

Andrew T DeWan (AT)

Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

Erik Solligård (E)

Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Helse Møre og Romsdal Hospital Trust, Ålesund, Norway.

Jan K Damås (JK)

Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Infectious Diseases, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Tormod Rogne (T)

Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
ORCID: 0000-0002-9581-7384

Classifications MeSH