Segregation analysis was performed on the serum uric acid measurements from 523 randomly ascertained Caucasian families from the NHLBI Family Heart Study. Gender-specific standardized residuals were used as the phenotypic variable in both familial correlation and segregation analysis. Uric acid residuals were adjusted for age, age2, age3, body mass index (kg/m2), creatinine level, aspirin use (yes/no), total drinks (per week), HOMA insulin resistance index [(glucose * insulin)/22.5], diuretic use (yes/no), and triglyceride level. Sibling correlations (r = 0.193) and parent-offspring correlations (r = 0.217) were significantly different from zero, but these two familial correlations were not significantly different from one another. After adjustment for covariates, the heritability estimate for serum uric acid was 0.399. Segregation analysis rejected the 'no major gene' model but was unable to discriminate between an 'environmental' and a 'Mendelian major gene' model. These results support the hypothesis that uric acid is a multifactorial trait possibly influenced by more than one major gene, modifying genes, and environmental factors.
Bibliographical noteFunding Information:
Acknowledgements This work was supported by cooperative agreements UO1 HL56563, UO1 HL 56564, UO1 HL 56565, UO1 HL 56566, UO1 HL 56567, UO1 HL 56568, UO1 HL 56569, from the National Heart, Lung, & Blood Institute, Bethesda, MD. This paper is presented on behalf of the Investigators of the NHLBI Family Heart Study. Participating Institutions and Principal Staff of the study are as follows: Forsyth County/University of North Carolina/Wake Forest University: Gerardo Heiss and Greg Evans/James Pankow/H.A. Tyroler, Jeannette T. Bensen, Catherine Paton, Delilah Posey, and Amy Haire; University of Minnesota Field Center: Aaron R. Folsom, James Peacock, Greg Feitl; Boston University/Framingham Field Center: R. Curtis Ellison, Yuqing Zhang, Andrew G. Bostom, and Greta Lee Splansky; University of Utah Field Center: Roger R. Williams (deceased), Paul N. Hopkins, Jan Skuppin and Hilary Coon; Coordinating Center, Washington University, St. Louis: Michael A. Province, Yuling Hong, Mary Feitosa, Jeanne Cashman, and Avril Adelman; Central Biochemistry Laboratory, University of Minnesota: Greg Rynders, Catherine Leiendecker-Foster, and Michael Y. Tsai; Central Molecular Laboratory, University of Utah: Mark F. Leppert, Jean-Marc Lalouel, Tena Varvil, Lisa Baird; National Heart, Lung, & Blood Institute – Project Office: Phylliss Sholinsky, Millicent Hig-gins (retired), Jacob Keller (retired), Sarah Knox, and Lorraine Silsbee. The results of this paper were obtained by using the program package S.A.G.E., which is supported by a US Public Health Service Resource Grant (1 P41 RR03655) from the National Center for Research Resources.
Copyright 2007 Elsevier B.V., All rights reserved.