Study of Over 20,000 Individuals Finds BMI Is Influenced by Different Genetic Factors That Change as We Age

Body mass index (BMI) is a quantitative measure that uses height and weight figures to determine whether an individual's mass is within a healthy range. Throughout their life, a person's BMI does not follow a linear trajectory – rather, it has three distinct periods of change. These periods are characterized by:

• a rapid increase in BMI up to the age of nine months [adiposity peak (AP)]
  
  
• a rapid decline in BMI up to the age of 5 to 6 years
  
  
• a steady increase until early adulthood, when BMI growth rate decelerates

Our height and weight are phenotypes influenced by a combination of genetic and lifestyle factors such as where we are from, what kinds of food we eat, and how often we exercise, for example.

Previous research has sought to characterize the genetic underpinnings of childhood and adult BMI, focusing on genetic variants influencing us through the ages of 2 to 18 years.

Tackling "globesity"

What research is yet to explore, is whether the changes in timing, velocity, or amplitude of the BMI trajectory during infancy and early childhood is influenced by specific genetic factors acting at different developmental stages.

As the world faces an escalating "globesity" crisis – where the numbers of overweight and obese individuals continue to grow – the identification of genetic determinants of early growth traits is fundamental, as it may provide insight into the etiology of obesity. Understanding this etiology opens the door for potential preventative strategies.

An international consortium of researchers led by scientists at Imperial College London have combined genome-wide association studies (GWAS) with modeling of longitudinal growth traits to study the genetics of infant and child growth. They have followed these assessments with functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. Their findings are published in the journal Science Advances.

The origins of obesity

In total, the researchers analyzed measures such as BMI and growth rates from 2 weeks to 13 years of age from more than 22,000 children and compared these to variations in their genome. They were therefore able to identify common genetic variants that are associated with the different peaks and troughs in BMI and their timings in the period of childhood.

The research study was conducted as part of the Early Growth Genetics Consortium, a collaborative effort that looks to combine data from multiple GWAS studies in order to identify additional human genome loci that impact a variety of traits related to early growth.

The Critical Nature of Adiposity rebound point

They found that the BMI of babies is influenced by a specific set of genetic variants that play little role in determining weight in later life. However, some genetic variants associated with adult BMI start playing a role during childhood, between the ages of four and seven. This finding supports that of previous research suggesting that the "adiposity rebound point" – when the BMI begins to steadily increase until early adulthood – is a key period for determining obesity in later life.

“Our study shows that nearly 100 genetic variants which increase a person’s risk of obesity in adulthood seem to start taking effect at an important stage of childhood development, from the age of around four,” said senior author Professor Marjo-Riitta Jarvelin, from Imperial’s School of Public Health. He continues: “We have shown that the origins of adult obesity lie in early childhood, and that there are clear windows across the life course which should be better considered in obesity prevention.”

Distinct biological processes driving BMI

The study also revealed a novel genetic variant that has an impact on infant BMI. This variant is in a region of the genome that contains the genes LEPR and LEPROT. The LEPR gene encodes the leptin receptor protein that is found on the surface of many cells in the body and is involved in the regulation of body weight via appetite control.

The novel variant does not appear to be associated with adult body weight regulation, and so the scientists suggest its effects may be limited to infancy: “It suggests there are distinct biological processes driving BMI in infancy compared to later in childhood and into adulthood,” says Jarvelin.

“We would like to further explore this variation in genetic makeup in infancy to better understand its role in development", Jarvelin concludes. The authors suggest that their study findings corroborate a model of BMI development consisting of the super-imposition of two biological processes with distinct genetic drivers.

Reference: Alves et al. 2019. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI. Sciences Advances.