The (not so stable) genetic risk of obesity – A mendelian randomization approach applied to obesity epidemiology

Room Manuel de Terán (3F8)
Institute of Economic, Geography and Demography
(CCHS-CSIC) C/ Albasanz, 26-28 Madrid 28037

Map

This event has been postponed.

Many genetic variants are associated with body mass index (BMI) – a measure of obesity.  Associations may have changed with the 20th century obesity epidemic and may differ for black vs white individuals. In an observational study of 8788 adults from the US national Health and Retirement Study with as many as 12 BMI assessments from 1992 to 2014. And using birth cohort as an indicator for exposure to obesogenic environment we evaluated whether genetic predisposition to higher BMI has a larger magnitude of association among adults from more recent birth cohorts, who were exposed to the obesity epidemic at younger ages

A multilocus genetic risk score for BMI (GRS-BMI), calculated as the weighted sum of alleles of 29 single nucleotide polymorphisms associated with BMI, with weights equal to the published per-allele effects. The GRS-BMI represents how much each person’s BMI is expected to differ, based on genetic background (with respect to these 29 loci), from the BMI of a sample member with median genetic risk.

The GRS-BMI, representing how much each person’s BMI is expected to differ, based on genetic background (with respect to these 29 loci), was significantly associated with BMI among white and black participants but accounted only for 0.99% of variation in BMI among white participants and 1.37% among black participants. In multilevel models accounting for age, the magnitude of associations of GRS-BMI with BMI were larger for more recent birth cohorts. For example, among white participants, each unit higher GRS-BMI was associated with a difference in BMI of 1.37 (95% CI, 0.93 to 1.80) if born after 1943, and 0.17 (95% CI, −0.55 to 0.89) if born before 1924 (P = .006). For black participants, each unit higher GRS-BMI was associated with a difference in BMI of 3.70 (95% CI, 2.42 to 4.97) if born after 1943, and 1.44 (95% CI, −1.40 to 4.29) if born before 1924.

For participants born between 1900 and 1958, the magnitude of association between BMI and a genetic risk score for BMI was larger among persons born in later cohorts. This suggests that associations of known genetic variants with BMI may be modified by obesogenic environments.

Lecturer

Stefan Walter holds a PhD in Public Health and Epidemiology from the Erasmus University, Rotterdam, The Netherlands. Currently, he is a researcher at Dept. of Medicine and Public Health at Rey Juan Carlos University, Madrid, where he is the Principal Investigator of the TALENT Advanced Grant “VIVIBRAIN” trail investigating the effect of physical activity on functional and brain ageing. Previously, he has worked as postdoctoral fellow at the Dept of Society, Human Development and Health at the Harvard School of Public Health and as a specialist for Mendelian Randomization Studies at the Dept. of Epidemiology and Biostatistics of the University of California San Francisco.