Identifying association under a previous linkage peak on chromosome 16 for body mass index using cross-sectional and...

We performed association analysis under a previous linkage peak on chromosome 16 with genome-wide single-nucleotide polymorphism (SNP) data to identify genetic variants underlying body mass index (BMI). Data from all subjects with baseline measures and a subgroup who had complete data at four selected time points from the Framingham Heart Study were analyzed. The cross-sectional measures include BMI at baseline for all subjects, as well as BMI at selected time points for the subgroup. The longitudinal measure is the within-subject mean of BMI for the subgroup at the four time points.Association analysis was first performed using PLINK after dividing large pedigrees into nuclear families. We then followed up the identified regions by variance-components methods as implemented in SOLAR using the extended pedigrees.The strongest evidence for associations were observed at 52.3 Mbp (PLINK p = 0.00002, QTLD p = 0.005), on the FTO gene, and at 48.1 Mbp (PLINK p = 0.002, QTLD p = 0.0006) on chromosome 16, which are directly under the previous identified linkage peak. This association was consistently observed for all samples at baseline, and for the subgroup at time point 2, 3, 4 and MEAN, both by PLINK and SOLAR. In addition, another SNP/region at 46.7 Mbp on same chromosome was found to be associated with several BMI measures in the subgroup. Fine-mapping with more markers provided further evidence for SNP association with BMI in the same region (at 52.4 Mbp, QTLD p = 0.0003).These results suggest the existence of genes/DNA variations in these regions that contribute to BMI variation.