Association of a genetic risk score with body mass index across several birth cohorts

Association of a genetic risk score with body mass index across several birth cohorts

1. This observational study found that BMI is associated with a genetic risk score calculated from multiple loci.

2. This association is present in both white and black cohorts, with the magnitude of the association strengthening in more recent birth cohorts.

Evidence Rating Level: 2 (Good)

Study Rundown: The obesity epidemic in the USA has impacted a significant proportion of the population, irrespective of race, age, and sex. While many environmental and behavioral factors have influenced this epidemic, genetics also likely plays a role. For instance, genetic factors may affect the metabolism of nutrients and could shape behavioral responses, like appetite and satiety. Previous studies have revealed that the environment in the USA has become more ‘obesogenic’ over time, and the authors of this study hypothesized that genetics likely affect our responses to such an environment. Utilizing genome wide association studies, this study calculated a polygenetic risk score for BMI (GRS-BMI) in successive birth cohorts of a national sample of US adults, and evaluated how the association with actual BMI changed over time. The results showed a correlation between GRS-BMI and actual BMI in both white and black cohorts. What’s more, the association has strengthened over time. Given that individuals born more recently have been exposed to the ‘obesogenic’ environment of the USA from a younger age, this result appears to confirm the authors’ primary hypothesis.

This observational study extends prior findings of genetic associations with obesity and supports the notion that genetic-environmental interactions affect obesity. However, the study is limited in a few key ways. Direct measures of the ‘obesogeneity’ of different environments were not performed, and the study did not take into account large historical events that may have influenced the results, such as the Great Depression. Additionally, the study relied on self-reported measurements of height and weight for BMI calculations, which may have introduced inaccuracies into the results. Overall, the study suggests that specific genetic variations can be modified by ‘obesogenic’ environments to affect BMI.

Click to read the study, pubilshed today in JAMA

Relevant Reading: The influence of age and sex on genetic associations with adult body size and shape.

In-Depth [retrospective cohort]: This study quantified the association between BMI and a polygenetic risk score for BMI in black and white US participants aged 50 years and older. The primary outcome measure was the self-reported height and weight of each participant, used to calculate BMI. Genetic samples were obtained from each participant, and a multilocus genetic risk score (GRS-BMI) was calculated based on a weighted sum of alleles of 29 single nucleotide polymorphisms. A total of 8788 subjects, born between 1900 and 1958, were studied and had their BMI assessed between 1992 and 2014.

The GRS-BMI was significantly associated with BMI among white (n = 7482; mean age at first assessment, 59 years, 45% male; p < 0.001), and black participants (n = 1306; mean age at first assessment, 57 years, 39% male; p < 0.001). The magnitude of the association was larger for more recent birth cohorts. In white participants born before 1924 each unit increase in GRS-BMI was associated with a BMI increase of 0.17 (95%CI -0.55 to 0.89), while those born after 1943 had a BMI increase of 1.37 (95%CI 0.93 to 1.80). Among black participants born before 1924 and after 1943 respectively, the association increased from 1.44 (95%CI -1.40 to 4.29) to 3.70 (95%CI 2.42 to 4.97).

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