Genotype-by-Sex Interaction in the Regulation of High-Density Lipoprotein: The Framingham Heart Study

Document Type

Article

Authors

M. J. Mosher, Department of Epidemiology, University of North Carolina at Chapel Hill, 137 E. Franklin Street, Suite 306 CB 8050, Chapel Hill, NC 27514.
L. J. Martin, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati School of Medicine, Cincinnati, OH.
L. A. Cupples, Department of Biostatistics, School of Public Health, Boston University, Boston, MA.
Q. Yang, Department of Biostatistics, School of Public Health, Boston University, Boston, MA.
T. D. Dyer, Southwest Foundation for Biomedical Research, San Antonio, TX.
J. T. Williams, Southwest Foundation for Biomedical Research, San Antonio, TX.
K. E. North, Department of Epidemiology, University of North Carolina at Chapel Hill, 137 E. Franklin Street, Suite 306 CB 8050, Chapel Hill, NC 27514.

Abstract

Low levels of high-density lipoprotein (HDL) are widely documented as a risk factor for cardiovascular disease (CVD). Furthermore, there is marked sexual dimorphism in both HDL levels and the prevalence of CVD. However, the extent to which genetic factors contribute to such dimorphism has been largely unexplored.We examined the evidence for genotypeby- sex effects on HDL in a longitudinal sample of 1,562 participants from 330 families in the Framingham Heart Study at three times points corresponding approximately to 1971–1974, 1980–1983, and 1988–1991. Using a variance component method, we conducted a genome scan of HDL at each time point in males and females, separately and combined, and tested for genotype-by-sex interaction at a quantitative trait locus (QTL) at each time point. Consistent findings were noted only for females on chromosome 2 near marker D2S1328, with adjusted LOD scores of 2.6, 2.2, and 2.1 across the three time points, respectively. In males suggestive linkage was detected on chromosome 16 near marker D16S3396 at the second time point and on chromosome 18 near marker D18S851 at the third time point (adjusted LOD 2.2 and 2.4, respectively). Although the heritability of HDL is similar in males and females, sex appears to exert a substantial effect on the QTL-specific variance of HDL. When genotype-by-sex interactions exist and are not modeled, the power to detect linkage is reduced; thus our results may explain in part the paucity of significant linkage findings for HDL.

Recommended Citation

Mosher, M. J.; Martin, L. J.; Cupples, L. A.; Yang, Q.; Dyer, T. D.; Williams, J. T.; and North, K. E. (2005) "Genotype-by-Sex Interaction in the Regulation of High-Density Lipoprotein: The Framingham Heart Study," Human Biology: Vol. 77: Iss. 6, Article 4.
Available at: https://digitalcommons.wayne.edu/humbiol/vol77/iss6/4