Abstract P367: Birth Weight Modifies the Association Between Central Nervous System Gene Variation and Adult Body Mass Index
Background: Genome wide association studies (GWAS) have identified 38 genetic loci associated with variation in body mass index (BMI) and weight. At least eleven of the identified BMI loci may be affecting body weight through their effects on the activity of the central nervous system (CNS). Persons with low birth weight have an increased risk of a series of metabolic disorders as adults, including alterations of CNS activity. We postulate that normal CNS-mediated genetic mechanisms of body weight regulation are disrupted in subjects with low birth weight.
Methods: We used general linear models to assess interaction between birth weight and CNS-gene variants in relation to BMI at age 18 and in 1995 in the Black Women’s Health Study (BWHS), an ongoing prospective cohort study that began in 1995. Birth weight was categorized as a binary variable (above and below the median, 3,200 g). We calculated a weighted CNS-gene score by summing the number of BMI-increasing alleles in 11 GWAS-identified CNS genes. Each SNP was weighted by its effect size based on results from meta-analyses in African ancestry populations. BMI was inverse-normally transformed after regressing on age and age squared. Models were adjusted for percentage of European ancestry. The present analyses include 2,596 BWHS participants with self-reported birth weight, genotype data on CNS genes, self-reported weight at age 18, and weight and height in 1995.
Results: CNS-gene score was associated with BMI residuals: beta-coefficient (95% CI) per BMI-increasing allele = 0.021 (0.0, 0.043) for BMI at age 18, and 0.022 (0.0, 0.044) for BMI in 1995. Among women with birth weight <3,200 g, there was no association between the CNS-gene score and BMI residuals: beta-coefficient (95% CI) per BMI-increasing allele = -0.005 (-0.035, 0.025) for BMI at age 18, and -0.001 (-0.031, 0.029) for BMI in 1995. Among women with birth weight ≥3,200 g, the CNS-gene score was positively associated with BMI residuals: beta-coefficient (95% CI) per BMI-increasing allele = 0.051 (0.020, 0.083) for BMI at age 18 (p for interaction = 0.011), and 0.049 (0.017, 0.080) for BMI in 1995 (p for interaction = 0.024). Similar results were observed when birth weight was categorized in quartiles.
Conclusions: CNS gene variants were not associated with adult BMI among women with birth weight <3,200 g, the median birth weight in our study population. Our results suggest that low birth weight may disrupt genetic mechanisms of CNS body weight regulation.
Author Disclosures: E.A. Ruiz-Narvaez: None. L. Rosenberg: None. J.R. Palmer: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.