Email updates

Keep up to date with the latest news and content from BMC Medical Genetics and BioMed Central.

This article is part of the supplement: The Framingham Heart Study 100,000 single nucleotide polymorphisms resource

Open Access Research

Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project

Caroline S Fox1*, Nancy Heard-Costa2, L Adrienne Cupples2, Josée Dupuis2, Ramachandran S Vasan2 and Larry D Atwood2

Author Affiliations

1 The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA

2 Boston University Schools of Medicine and Public Health, Boston, MA, USA

For all author emails, please log on.

BMC Medical Genetics 2007, 8(Suppl 1):S18  doi:10.1186/1471-2350-8-S1-S18

Published: 19 September 2007

Abstract

Background

Obesity is related to multiple cardiovascular disease (CVD) risk factors as well as CVD and has a strong familial component. We tested for association between SNPs on the Affymetrix 100K SNP GeneChip and measures of adiposity in the Framingham Heart Study.

Methods

A total of 1341 Framingham Heart Study participants in 310 families genotyped with the Affymetrix 100K SNP GeneChip had adiposity traits measured over 30 years of follow up. Body mass index (BMI), waist circumference (WC), weight change, height, and radiographic measures of adiposity (subcutaneous adipose tissue, visceral adipose tissue, waist circumference, sagittal height) were measured at multiple examination cycles. Multivariable-adjusted residuals, adjusting for age, age-squared, sex, smoking, and menopausal status, were evaluated in association with the genotype data using additive Generalized Estimating Equations (GEE) and Family Based Association Test (FBAT) models. We prioritized mean BMI over offspring examinations (1–7) and cohort examinations (10, 16, 18, 20, 22, 24, 26) and mean WC over offspring examinations (4–7) for presentation. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg equilibrium p ≥ 0.001, and call rates of at least 80%.

Results

The top SNPs to be associated with mean BMI and mean WC by GEE were rs110683 (p-value 1.22*10-7) and rs4471028 (p-values 1.96*10-7). Please see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite for the complete set of results. We were able to validate SNPs in known genes that have been related to BMI or other adiposity traits, including the ESR1 Xba1 SNP, PPARG, and ADIPOQ.

Conclusion

Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.