Sex and Age Specific Effects of Chromosomal Regions Linked to Body Mass Index in the Framingham Study

BACKGROUND: Previously, we reported significant linkage of body mass index (BMI) to chromosomes 6 and 11 across six examinations, covering 28 years, of the Framingham Heart Study. These results were on all individuals available at each exam, thus the sample size varied from exam to exam. To remove any effect of sample size variation we have now constructed six subsets; for each exam individuals were only included if they were measured at every exam, i.e. for each exam, included individuals comprise the intersection of the original six exams. This strategy preferentially removed older individuals who died before reaching the sixth exam, thus the intersection datasets are smaller (n = 1114) and significantly younger than the full datasets. We performed variance components linkage analysis on these intersection datasets and on their sex-specific subsets. RESULTS: Results from the sex-specific genome scans revealed 11 regions in which a sex-specific maximum lodscore was at least 2.0 for at least one dataset. Randomization tests indicated that all 11 regions had significant (p < 0.05) differences in sex-specific maximum lodscores for at least three datasets. The strongest sex-specific linkage was for men on chromosome 16 with maximum lodscores 2.70, 3.00, 3.42, 3.61, 2.56 and 1.93 for datasets 1–6 respectively. Results from the full genome scans revealed that linked regions on chromosomes 6 and 11 remained significantly and consistently linked in the intersection datasets. Surprisingly, the maximum lodscore on chromosome 10 for dataset 1 increased from 0.97 in the older original dataset to 4.23 in the younger smaller intersection dataset. This difference in maximum lodscores was highly significant (p < 0.0001), implying that the effect of this chromosome may vary with age. Age effects may also exist for the linked regions on chromosomes 6 and 11. CONCLUSION: Sex specific effects of chromosomal regions on BMI are common in the Framingham study. Some evidence also exists for age-specific effects of chromosomal regions.National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK066241); Framingham Heart Study of National Heart Lung and Blood Institute (HC-25195