Cover: Influence of SNP*SNP Interaction on BMI in European American Adolescents

Influence of SNP*SNP Interaction on BMI in European American Adolescents

Findings from the National Longitudinal Study of Adolescent Health

Published in: Pediatric Obesity, Volume 11, Issue 2, pages 95-101 (April 2016). doi: 10.1111/ijpo.12026

Posted on rand.org Nov 9, 2023

by Kristin L. Young, Misa Graff, Kari E. North, Andrea S. Richardson, Jonathan P. Bradfield, Struan F. A. Grant, Leslie A. Lange, Ethan M. Lange, Kathleen Mullan Harris, Penny Gordon-Larsen

Background

Adolescent obesity is predictive of future weight gain, obesity and adult onset severe obesity (body mass index [BMI] ≥40 kg m−2). Despite successful efforts to identify Single Nucleotide Polymorphisms (SNPs) influencing BMI, <5% of the 40–80% heritability of the phenotype has been explained. Identification of gene–gene (G-G) interactions between known variants can help explain this hidden heritability as well as identify potential biological mechanisms affecting weight gain during this critical developmental period.

Objective

We have recently shown distinct genetic effects on BMI across the life course, and thus it is important to examine the evidence for epistasis in adolescence.

Methods

In adolescent participants of European descent from wave II of the National Longitudinal Study of Adolescent Health (Add Health, n = 5072, ages 12–21, 52.5% female), we tested 34 established BMI-related SNPs for G-G interaction effects on BMI z-score. We used mixed-effects regression, assuming multiplicative interaction models adjusting for age, sex and geographic region, with random effects for family and school.

Results

For 28 G-G interactions that were nominally significant (P < 0.05), we attempted to replicate our results in an adolescent sample from the Childhood European American Cohort from Philadelphia. In the replication study, one interaction (PRKD1-FTO) was significant after correction for multiple testing.

Conclusions

Our results are suggestive of epistatic effects on BMI during adolescence and point to potentially interactive effects between genes in biological pathways important in obesity.

Research conducted by

This report is part of the RAND external publication series. Many RAND studies are published in peer-reviewed scholarly journals, as chapters in commercial books, or as documents published by other organizations.

RAND is a nonprofit institution that helps improve policy and decisionmaking through research and analysis. RAND's publications do not necessarily reflect the opinions of its research clients and sponsors.