Genes Linked to Higher BMI in Obesogenic Environments

Becky McCall

July 11, 2016

People born around the middle of the 20th century have a greater association between genes and high body mass index (BMI) than those born earlier in the century, shows a study of the US population who entered an obesity epidemic in the mid-1970s.

The findings, published in July 5 issue of the Journal of the American Medical Association by Stefan Walter, PhD, of the University of California, San Francisco (UCSF), and colleagues, suggest that associations of known genetic variants with high BMI may be modified by obesogenic environments.

In essence, the study asked whether the association between someone's genes for BMI and actual BMI differed between individuals who were younger or older when the US obesity epidemic began. Unlike previous similar studies, a key strength of this work was the diversity of population, which features black and white US adults born between 1900 and 1958.

"People who were born early in the last century were older by the time the obesity epidemic began, and we expected that the genetic risk for [high] BMI would have a smaller impact on their BMI than those who were younger when the epidemic started, who have therefore lived more of their life in an obesogenic environment," explained senior author Maria Glymour, ScD, of the department of epidemiology and biostatistics, UCSF.

She also highlighted the fact that, whether genetic risk was high or low, BMI was increased in people born more recently. "Even those participants with low genetic risk were affected by the obesity epidemic," she said, emphasizing the role of the environment regardless of genetic risk.

"Environmental factors are the biggest determinants of obesity, and importantly this is something that people can change."

Birth Year Key Indicator of Exposure to Obesogenic Environment

In designing the study, researchers wanted to use a powerful environmental determinant of obesity risk and decided that the year of birth was strong in this respect, given the surge in prevalence of obesity since the mid-to-late 1970s in the US. “We felt that the year someone was born provided an indicator of how exposed people were to an obesogenic environment,” said Dr Glymour.

Numerous genetic variants have been shown to influence BMI, although each genetic polymorphism has a small impact when considered by itself.

"We asked whether, for those genetic factors that are known to relate to obesity status, the importance of these genes is really dependent on the environment someone is born in, as indicated by the year of birth," Dr Glymour noted.

The observational study drew data from 8788 adults from the US-based Health and Retirement Study (HRS). In total, 7482 white participants with a mean age of 59 years were included, 45% of whom were men. There were fewer black participants: 1306 were included with a mean age of 57 years, 39% of whom were men.

A genetic risk score (GRS) for BMI was calculated for each participant and represented how much an individual's BMI was expected to differ ― based on 29 genetic variants (single-nucleotide polymorphisms [SNPs]) known to be associated with high BMI ― from the BMI of a sample member with median genetic risk.

Up to 14 assessments of BMI were carried out for each participant from 1992 to 2014. Each participant's GRS-BMI was calculated in relation to their BMI, and after researchers controlled for age, an association was calculated for their genetic risk and actual BMI. Variation in this association was recorded across birth cohorts.

Environment Greatly Affects Genetic Risk of Obesity

Among both black and white participants, genetic risk for high BMI was found to be significantly associated with BMI (both P < .001). However, genetic risk accounted for 1.37% of variation in BMI among black participants and 0.99% among white participants.

After adjustment for age, the size of the association of genetic risk and BMI was larger for more recent birth cohorts, such that among white participants, each unit higher genetic risk was associated with a difference in BMI of 1.37 if a person was born after 1943, but only 0.17 for those born before 1924 (P = .006).

For black participants, this effect was even greater ― each unit higher genetic risk was associated with a 3.70 difference in BMI if a person born after 1943, but only 1.44 for those born before 1924.

"In this study, we were really excited to find such a large modification of risk in a diverse population including both black and white people," Dr Glymour commented.

She added that this demonstrates that the importance of genes really depends on the environment. "Even if you have high genetic risk, in the healthiest environment there is very little obesity. Effectively, the relevance of your genetic profile is filtered by the environment you live in."

In future, the researchers would like to look at how environmental factors modify the effects of genetic risk for other major chronic diseases, such as diabetes and Alzheimer's disease, and to look at populations outside the United States where the patterns of the obesity epidemic are different.

"Looking at the effects of genes in diverse environments can give a more accurate sense of the importance of environmental factors in determining risk of disease," Dr Glymour concluded.

The authors report no relevant financial relationships.

JAMA. 2016;316:63-69. Abstract

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