Abstract

ObjectiveTo test transethnic replication of a genetic risk score for obesity in white and black young adults using a national sample with longitudinal data.Design and MethodsA prospective longitudinal study using the National Longitudinal Study of Adolescent Health Sibling Pairs (n = 1,303). Obesity phenotypes were measured from anthropometric assessments when study members were aged 18–26 and again when they were 24–32. Genetic risk scores were computed based on published genome-wide association study discoveries for obesity. Analyses tested genetic associations with body-mass index (BMI), waist-height ratio, obesity, and change in BMI over time.ResultsWhite and black young adults with higher genetic risk scores had higher BMI and waist-height ratio and were more likely to be obese compared to lower genetic risk age-peers. Sibling analyses revealed that the genetic risk score was predictive of BMI net of risk factors shared by siblings. In white young adults only, higher genetic risk predicted increased risk of becoming obese during the study period. In black young adults, genetic risk scores constructed using loci identified in European and African American samples had similar predictive power.ConclusionCumulative information across the human genome can be used to characterize individual level risk for obesity. Measured genetic risk accounts for only a small amount of total variation in BMI among white and black young adults. Future research is needed to identify modifiable environmental exposures that amplify or mitigate genetic risk for elevated BMI.

Highlights

  • Genome-wide association studies (GWAS) have discovered genetic loci that associate with obesity risk [1]

  • White and black young adults with higher genetic risk scores had higher BMI and waist-height ratio and were more likely to be obese compared to lower genetic risk age-peers

  • Sibling analyses revealed that the genetic risk score was predictive of BMI net of risk factors shared by siblings

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Summary

Introduction

Genome-wide association studies (GWAS) have discovered genetic loci that associate with obesity risk [1]. Genetic risks manifest early in life; children at higher genetic risk gain weight more rapidly during infancy and early childhood and reach adiposity rebound earlier in life and at higher body-mass-index (BMI) [2,3,4]. This rapid growth early in life functions as a mediator of genetic risk for adult obesity [4]. Combining information on multiple GWAS discovered SNPs to compute a ‘‘genetic risk score’’ can provide a tool for investigating genetic contributions to obesity etiology in samples far smaller than are needed for GWAS [8,9]

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