The relationship between sex hormone-binding globulin (SHBG) concentrations and body fat accumulation and distribution is governed by complex dynamic factors, which may involve common genetic and/or environmental factors. The current study investigated the genetic and environmental basis for the correlation between SHBG and body fat. Several measures of adiposity were investigated including body mass index (BMI) and a trunk to extremity skinfold thickness ratio (TER) assessed by anthropometry, body composition measured by hydrostatic weighing (total body fat mass [FM], fat-free mass [FFM], and percent body fat [%BF]), and abdominal fat measured by computerized tomography scanning (abdominal visceral fat [AVF]). The study comprised 501 white subjects from 99 families and 277 black subjects from 117 families participating in the HERITAGE Family Study. Familial correlations between traits and their cosegregation were investigated both at baseline and in response to endurance exercise training. Significant inverse phenotypic correlations were detected in both races between SHBG and adiposity measures at baseline and also in response to training. Significant cross-trait familial resemblance was found between SHBG and both BMI and FFM at baseline that accounted for 11% and 4% of maximal heritability, respectively, in white families. However, a joint segregation analysis of the traits failed to implicate shared genetic effects. Specifically, neither a pleiotropic major locus nor pleiotropic polygenic effects were detected between SHBG and BMI or FFM. A maximal cross-trait heritability of 45% was obtained for SHBG and TER at baseline in black families. However, no firm conclusions as to the etiology of this relationship could be drawn because of the limitations of small sample size. For the training response phenotypes, there was no significant cross-trait correlation between SHBG and any adiposity measures studied here, suggesting that their correlation may have an environmental basis. Therefore, this study fails to support the hypothesis of genetic pleiotropy between SHBG concentrations and body fat phenotypes, and suggests an environmental basis for the correlation, ie, SHBG concentrations are genetically independent of body composition and abdominal adiposity phenotypes.
Bibliographical noteFunding Information:
Supported by Grants No. HL45670 (to C.B.), HL47323 (to A.S.L.), HL47317 (to D.C.R.), HL47327 (to J.S.S.), and HL47321 (J.H.W.) from the National Heart, Lung, and Blood Institute and by a grant from the National Institutes of Health (NIH) to the University of Minnesota Clinical Research Center. A.S.L. is also supported in part by the Henry L. Taylor Professorship in Exercise Science and Health Enhancement. C.B. also is partially supported by the George A. Bray Chair in Nutrition.