Adiposity and infection-related mortality: Mendelian randomisation study of 126,000 Mexican adults

Journal article

Background:
The causal relevance of different adiposity markers to infection-related death remains uncertain. We estimated lifelong associations of genetically-predicted adiposity traits with infection-related mortality among 126,491 Mexican adults.
Methods:
Mendelian randomisation (MR) using trans-ancestry instruments for body mass index (BMI), fat mass percentage (FM%), and waist and hip circumference estimated causal effects on infection-related mortality at ages 35-74 years, overall and across six infection subtypes. Multivariable MR assessed independent associations.
Results:
Genetic instruments explained 1.6–3.5% of variance in adiposity markers and the strengths of their associations with the markers were similar in men and women. Over 20 years, 2592 infection-related deaths occurred at ages 35-74 years. Genetically-predicted adiposity was strongly associated with infection mortality, with the strongest association for FM% (hazard ratio [HR] per 1SD higher level: 2.54; 95% CI 1.91-3.38) and the weakest for hip circumference (1.61; 1.30-2.01). Associations were consistent across six subtypes: respiratory; urinary tract; gastrointestinal; sepsis; skin, bone and connective tissue; and other infections. For BMI and FM%, mutual adjustment for waist and hip circumference reduced the associations by nearly one third. For waist circumference, adjustment for BMI and hip circumference reduced the association by more than one half, while for hip circumference, mutual adjustment for BMI and waist circumference almost eliminated its association. Sensitivity analyses supported the main conclusions.
Conclusion:
Higher adiposity is causally associated with higher risk of infection related mortality in Mexican adults. Strategies to reduce population levels of adiposity in Mexico could contribute to lowering mortality from infection.

Authors: Lawal, L; Trichia, E; Alegre-Díaz, J; Baca, P; Barerra, E

• Publication status: Accepted
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: International Journal of Epidemiology
• Acceptance date: 2026-08-19
• EISSN: 1464-3685
• ISSN: 0300-5771
• Language: English
• Keywords: adiposity; infection; Mexico; Mendelian randomisation