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Heritability of Plasma Sex Hormones and Hormone Binding Globulin in Adult Male Twins

Center for Health Sciences (H.Z.R., C.N.L., G.E.S., D.C.), SRI International, Menlo Park, California 94025; Department of Medical and Molecular Genetics (T.R.), Indiana University School of Medicine, Indianapolis, Indiana 46202; and Department of Medicine (R.M., L.H.), Stanford University School of Medicine, The Geriatrics Research, Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304

Address all correspondence and requests for reprints to: Huijun Z. Ring, Ph.D., Center for Health Sciences, SRI International, 333 Ravenswood Avenue, Menlo Park, California 94025. E-mail: huijun.ring{at}sri.com.

Plasma sex hormone concentrations have been used as biomarkers in epidemiological studies of many conditions including cancer, obesity, bone density, and coronary heart disease. The objective of this analysis was to estimate genetic and nongenetic influences on endogenous sex hormones (testosterone, estradiol, estrone, and SHBG) in a large sample of 532 adult white male twins (134 monozygotic and 132 dizygotic twin pairs) from the National Heart, Lung, and Blood Institute Twin Study. Participants were aged 59–70 yr at the time of plasma collection, and hormone concentrations were determined with RIA. Genetic models were fitted by the method of maximum likelihood. Testosterone and SHBG concentrations have substantial genetic variation, with additive genetic factors accounting for 57 and 68% of the total phenotypic variation, respectively. In contrast, variation in estrone (37% shared environmental and 63% individual specific environmental effects) and estradiol concentrations (25% genetic effect, 44% shared environmental effects, and 31% individual specific environmental effects) were largely influenced by nongenetic factors. Assessment of the relative contribution of genetic and nongenetic influences on hormone concentrations may help in the search for genes underlying variation and covariation in complex traits affected by plasma sex hormone concentrations.

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