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. 2014 Mar;22(3):875-81.
doi: 10.1002/oby.20517. Epub 2013 Aug 13.

Gene-by-age effects on BMI from birth to adulthood: the Fels Longitudinal Study

Audrey C Choh  1 , Miryoung Lee, Jack W Kent, Vincent P Diego, William Johnson, Joanne E Curran, Thomas D Dyer, Claire Bellis, John Blangero, Roger M Siervogel, Bradford Towne, Ellen W Demerath, Stefan A Czerwinski
Affiliations

Gene-by-age effects on BMI from birth to adulthood: the Fels Longitudinal Study

Audrey C Choh et al. Obesity (Silver Spring). 2014 Mar.

Abstract

Objectives: Genome wide association studies have shown 32 loci to influence BMI in European-American adults but replication in other studies is inconsistent and may be attributed to gene-by-age effects. The aims of this study were to determine if the influence of the summed risk score of these 32 loci (GRS) on BMI differed across age from birth to 40 years, and to determine if additive genetic effects other than those in the GRS differed by age.

Methods: Serial measures of BMI were calculated at 0, 1, 3, 6, 9, 12, 18, and 28 months, and 4, 7, 11, 15, 19, 23, 30, and 40 years for 1,176 (605 females, 571 males) European-American participants in the Fels Longitudinal Study. SOLAR was used for genetic analyses.

Results: GRS was significant (P < 0.05) at ages: 6, 9 months, 4-15 years, and 23-40 years. Remaining additive genetic effects independently influenced BMI (P < 5.3 × 10(-5) , 0.40 < h(2) < 0.76). Some genetic correlations between ages were not significant. Differential GRS effects did not retain significance after multiple comparisons adjustments.

Conclusions: While well-known BMI variants do not appear to have significant differential effects, other additive genes differ over the lifespan.

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Conflict of interest statement

DISCLOSURES

The authors have no conflicts of interest to declare.

The authors have no competing interests.

Figures

FIGURE 1
FIGURE 1
Mean BMI (solid squares, left axis) and influence of BMI variants (diamonds, right axis) across age at birth, infancy (1, 3, 6, 9, 12, 18, and 28 months) childhood (4 and 7 years), adolescence (11 and 15 years), adulthood (19, 23, and 30 years) and mid-adulthood (40 years). βGRS is significantly different from zero (p < 0.05) at 6 and 9 months, all of childhood and adolescence, and at ages 23, 30 and 40 years (solid diamonds).
FIGURE 2
FIGURE 2
Proportion of the variance explained by BMI variants (open squares, right axis) and additive genetic effects (h2) adjusting for BMI variants (solid squares, left axis), across age at birth, infancy (1, 3, 6, 9, 12, 18, and 28 months) childhood (4 and 7 years), adolescence (11 and 15 years), adulthood (19, 23, and 30 years) and mid-adulthood (40 years). All heritability estimates were significant (p < 5.3×10−5).
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