Genes Influence Body Fat More Than Lean Mass

10/05/2022

The study covered in this summary was published on medRxiv as a preprint and has not yet been peer reviewed.

Key Takeaways

Genetic variants — single-nucleotide polymorphisms (SNPs) indicating susceptibility to having larger body size in childhood and other SNPs indicating susceptibility to having larger body size in adulthood — were associated more strongly with adiposity than with lean mass in a longitudinal study of English individuals who underwent surveillance six times during the period when they were 9 to 25 years old.
Among girls and women, genetic variants for larger childhood body size were associated more strongly with adiposity than genetic variants for larger adult body size during childhood and adolescence.
Among boys and men, genetic variants for larger childhood body size and genetic variants for larger adult body size showed similar degrees of association with adiposity during the first decades of life.

Why This Matters

Gaining a better understanding of the life stage–specific and sex-specific genomic components of adiposity could lead to strategies to prevent obesity, such as genotyping children at an early age, monitoring genetic risk over time, and providing targeted health advice.
Future studies that extend the current study into later adulthood could help determine when genetic variants for adult body size become more influential than genetic variants for childhood body size and whether genetic risks for childhood adiposity influence body composition later in life.

Study Design

The researchers analyzed data from 3511 girls and women and 3415 boys and men from the Avon Longitudinal Study of Parents and Children birth cohort, in Bristol, United Kingdom. The study cohort included White persons and first-born children from among 13,998 individuals born from 1991 to 1992.
The cohort underwent genetic testing to determine sex-specific genetic risk scores (GRSs) for childhood and adult body size. In calculating GRS, the researchers relied on published sex-specific genome-wide association studies that had identified 134 SNPs and 212 SNPs associated with childhood and adult body size, respectively, in girls and women and 69 SNPs and 158 SNPs associated with childhood and adult body size, respectively, in boys and men.
The study subjects underwent whole-body dual-energy x-ray absorptiometry (DXA) scans to measure total, trunk, and peripheral (arms + legs) fat mass and total lean mass at ages 9, 11, 13, 15, 18, and 25 years.
The researchers examined the sex-specific associations of GRS with trajectories of fat mass and lean mass for ages 9 to 25 years.

Key Results

Among boys and men, childhood and adulthood GRS was associated with similar differences in fat mass from ages 9 to 18 years. At age 25 years, the association of childhood GRS with fat mass attenuated, whereas adulthood GRS associations remained relatively similar to observations at age 18 years.
Among girls aged 9 to 18 years, associations of the childhood GRS with fat mass were almost twofold stronger than associations of the adulthood GRS with fat mass. Among women aged 25 years, associations were similar between their childhood and adulthood GRS and fat mass.
The associations between GRS and lean mass were much smaller in both sexes.

Limitations

The study subjects were White Europeans with high socioeconomic backgrounds, and the findings may not be generalizable to other races, ethnicities, or populations.
Although the DXA measures that quantified fat and lean mass are better than indirect measures such as body mass index or waist circumference, they are less precise than MRI, they cannot be used to assess ectopic fat, and they may not be equally precise across a range of body mass index values.
The data were longitudinal, and nonrandom loss to follow-up may have biased the results.

Disclosures

The genome analysis received funding support from 23andMe.
The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Life Stage-Specific Effects of Genetic Susceptibility to Higher Body Size on Body Fat and Lean Mass: Prospective Cohort Study,” written by researchers affiliated with the University of Bristol, UK, published on medRxiv, and provided to you by Medscape. This study has not yet been peer reviewed. The full study text can be found on medrxiv.org.

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