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

The causal relevance of different adiposity markers to infection-related death remains uncertain. We estimated the lifelong associations of genetically predicted adiposity traits with infection-related mortality among 126 491 Mexican adults.

Mendelian randomization (MR) using trans-ancestry instruments for body mass index (BMI), fat-mass percentage (FM%), and waist and hip circumference was used to estimate causal effects on infection-related mortality at ages 35-74 years, overall and across six infection subtypes. Multivariable MR was used to assess independent associations.

Genetic instruments explained 1.6%-3.5% of the 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 1-SD higher level: 2.54; 95% confidence interval (CI) 1.91-3.38] and the weakest for hip circumference (HR 1.61; 95% CI 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 half, while, for hip circumference, mutual adjustment for BMI and waist circumference almost eliminated its association. Sensitivity analyses supported the main conclusions.

Higher adiposity is causally associated with a higher risk of infection-related mortality in Mexican adults. Strategies to reduce the population levels of adiposity in Mexico could contribute to lowering mortality from infection.