Estimation of genetic effects on BMI during adolescence in an ethnically diverse cohort: The National Longitudinal Study of Adolescent Health

Abstract

Objective: The contribution of genetic variants to body mass index (BMI) during adolescence across multiethnic samples is largely unknown. We selected genetic loci associated with BMI or obesity in European-descent samples and examined them in a multiethnic adolescent sample.

Design and sample: In 5103 European American (EA), 1748 African American (AfA), 1304 Hispanic American (HA) and 439 Asian American (AsA) participants of the National Longitudinal Study of Adolescent Health (Add Health; ages 12-21 years, 47.5% male), we assessed the association between 41 established obesity-related single-nucleotide polymorphisms (SNPs) with BMI using additive genetic models, stratified by race/ethnicity, and in a pooled meta-analysis sample. We also compared the magnitude of effect for BMI-SNP associations in EA and AfA adolescents to comparable effect estimates from 11 861 EA and AfA adults in the Atherosclerosis Risk in Communities study (ages 45-64 years, 43.2% male).

Results: Thirty-five of 41 BMI-SNP associations were directionally consistent with published studies in European populations, 18 achieved nominal significance (P<0.05; effect sizes from 0.19 to 0.71 kg m(-2) increase in BMI per effect allele), while 4 (FTO, TMEM18, TFAP2B, MC4R) remained significant after Bonferroni correction (P<0.0015). Of 41 BMI-SNP associations in AfA, HA and AsA adolescents, nine, three and five, respectively, were directionally consistent and nominally significant. In the pooled meta-analysis, 36 of 41 effect estimates were directionally consistent and 21 of 36 were nominally significant. In EA adolescents, BMI effect estimates were larger (P<0.05) for variants near TMEM18, PTER and MC4R and smaller for variants near MTIF3 and NRXN3 compared with EA adults.

Conclusion: Our findings suggest that obesity susceptibility loci may have a comparatively stronger role during adolescence than during adulthood, with variation across race/ethnic subpopulation.

Figure 1

Add Health study population.

Figure 2

Forty-one SNPs previously associated with obesity, BMI or central adiposity phenotypes in European-descent adults, are plotted according to directional consistency (compared with previous findings in adults of European descent) of effect estimates with BMI in each of the four race/ethnic groups within the National Longitudinal Study of Adolescent Health. BMI SNPs have shown in black and obesity SNPs shown in red. ¹rs4788102, ²rs10913469, ³rs7359397, ⁴rs543874, ⁵rs571312, ⁶rs12970134.

Figure 3

Effect sizes of BMI loci for European Americans in the Add Health adolescent cohort compared with the findings in adults. Z-test used to compare effect sizes of Add Health adolescents and ARIC adults: . Of 41 comparisons, the SNPs displayed are those with P-value for differences <0.10, sorted from largest to smallest effect estimates in Add Health adolescents. *P<0.05 for difference, ^†P<0.1 for difference.