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Background  Despite strong evidence for a genetic component to variation in high-density lipoprotein cholesterol levels (HDL-C), specific polymorphisms associated with normal variation in HDL-C have not been identified. It is known, however, that HDL-C levels are influenced in complex ways by factors related to age and sex. In this paper, we examined the evidence for age- and sex-specific linkage of HDL-C in a longitudinal sample of participants from the Framingham Heart Study.  To determine if aging could influence our ability to detect linkage, we explored the evidence for linkage of HDL-C at three time points,  t  1 ,  t  2 , and  t  3 , spaced approximately 8 years apart and corresponding respectively to visits 11, 15, and 20 for the original cohort and 1, 2, and 4 for the offspring and spouses. Additionally, to examine the effects of sex on linkage at each time point, we estimated the heritability and genetic correlation of HDL-C, performed linkage analysis of HDL-C, tested for genotype-by-sex interaction at a QTL, and performed linkage analysis of HDL-C in males and females separately.    Results and Conclusion  In women, we found evidence for a QTL on chromosome 2q influencing HDL-C variation. Although the QTL could be detected in the combined sample of males and females at the first time point, the linkage was not significant at subsequent time points.

HDL cholesterol in females in the Framingham Heart Study is linked to a region of chromosome 2q