NEW YORK – Different genetic factors influence people's body mass index during infancy compared to later in life, a new genome-wide association study has found.
For a new study appearing in Science Advances today, researchers from the Early Growth Genetics Consortium conducted a GWAS of six different early growth traits, including BMI at about nine months and at five to six years of age. While they uncovered overlap been the genetic variants that influence BMI during childhood and adulthood, different ones appear to affect BMI during infancy.
"It suggests there are distinct biological processes driving BMI in infancy compared to later in childhood and into adulthood," senior author Marjo-Riitta Jarvelin, a professor at Imperial College London's School of Public Health, said in a statement.
Both genetic and environmental factors influence people's BMI, which fluctuates throughout life. It typically increases quickly from birth until about nine months of age — peak adiposity — when it declines until about the age of five or six — adiposity rebound — and then increases until adulthood. Adiposity rebound is thought to be a key time for determining later-in-life risk of obesity.
In their study, the consortium researchers examined longitudinal and genetic data collected on more than 22,000 children. Their two-stage meta-analysis focused on six early growth traits: peak height velocity, peak weight velocity, age at adiposity peak, BMI at adiposity peak, age at adiposity rebound, and BMI at adiposity rebound. Through this, they linked common variants at four loci to one or more of the growth traits.
Three of these four loci were associated with both age at adiposity rebound and BMI at adiposity rebound and were previously linked to adult BMI, adult weight, and other adiposity-linked phenotypes.
One variant associated with BMI at peak adiposity was novel and is located in the same locus as the LEPR/LEPROT gene, which encodes the leptin receptor and the leptin receptor overlapping transcript. In adults, this region is involved in regulating the hormone leptin, which is produced by fat cells and reduces appetite. However, they added that this variant does not appear to influence adult weight regulation.
While age at adiposity rebound and BMI at adiposity rebound had moderate-to-strong genetic correlations with adult BMI and other adult adiposity-linked phenotypes such as waist circumference and body fat percentage, the researchers noted that BMI at peak adiposity did not.
Based on an analysis using an adult BMI genetic risk score they devised from Genetic Investigation of Anthropometric Traits consortium findings, the researchers found that both the adult BMI-linked variants and this genetic risk score were associated with age at adiposity rebound, but not with other early growth traits. This suggested to the researchers that many variants that influence adult BMI begin to have an effect early in life, as early as age at adiposity rebound at about five or six years of ages, but not as early as age at peak adiposity, about nine months of age.
Instead, through a gene set analysis, they reported that different genetic networks appear to influence age at peak adiposity, as compared to age at adiposity rebound.
If the researchers could further tease out the biological processes that influence BMI during infancy, they could begin to understand risk factors associated with the later development of obesity. "If we can explain what is happening in early life, then we can start to understand why some people become obese and some people don't even though they are eating the same amount of calories," Jarvelin said. "This may allow us to tackle the risk factors that are leading to the obesity epidemic."