This Article Full Text Full Text (PDF) All Versions of this Article: 92/8/3171    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Livshits, G. Articles by Spector, T. D. Search for Related Content PubMed PubMed Citation Articles by Livshits, G. Articles by Spector, T. D. Related Collections Female Endocrinology Metabolism

Linkage of Genes to Total Lean Body Mass in Normal Women

Sackler Faculty of Medicine (G.L.), Tel Aviv University, Tel Aviv 69978, Israel; Twin Research and Genetic Epidemiology (G.L., B.S.K., T.D.S.), Unit St. Thomas’ Hospital, Kings College London, London SE1 7EH, United Kingdom; and Department of Endocrinology and Diabetes (S.G.W.), Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009

Address all correspondence and requests for reprints to: Tim D. Spector, Twin Research and Genetic Epidemiology Unit, St. Thomas’ Hospital, Kings College London, London SE1 7EH, United Kingdom. E-mail: tim.spector{at}kcl.ac.uk.

Background: Total lean body mass (LEAN-tot) is one of the three major components of body weight. Its deterioration is a risk factor for frailty. Despite this, there are few studies examining the contribution of genetic factors.

Objective: Our objective was to examine the contribution of genetic factors for LEAN-tot variation, including a genome-wide search for the genes.

Research Methods: Dual-energy x-ray absorptiometry measurements of LEAN-tot were obtained from each of the 3180 United Kingdom females (509 monozygotic and 1081 dizygotic twin pairs). Contribution of genetic factors was assessed using variance component analysis. A genome-wide linkage analysis was performed on the dizygotic twins using a modified version of the Haseman-Elston method.

Results: Age, body height, total fat, and bone mass were correlated with LEAN-tot, and commonly explained 52% of the LEAN-tot variation. The crude heritability estimate was 74.0 ± 4.0%, after adjustment for the aforementioned factors; 65.2 ± 4.6% was attributable to independent genetic effects. Significant (P < 0.001) genetic correlations were found between LEAN-tot and bone mass, and LEAN-tot and total fat. Adjusted only for age, LEAN-tot showed no significant linkage. After adjustment for all covariates, significant linkage (LOD = 4.49 and 3.62) was observed at chromosome 12q24.3 and 14q22.3, respectively. Additional peaks of interest were on 7p15.3-15.1 (LOD = 2.86) and 8p22 (LOD = 2.83).

Conclusions: LEAN-tot measured by dual-energy x-ray absorptiometry is highly heritable, independent of other body measures. This first genomic search for genes associated with the lean component of body mass suggests significant linkage to quantitative trait loci on chromosomes 12 and 14.

This article has been cited by other articles:

				F. E. Dewey, D. Rosenthal, D. J. Murphy Jr, V. F. Froelicher, and E. A. Ashley Does Size Matter?: Clinical Applications of Scaling Cardiac Size and Function for Body Size Circulation, April 29, 2008; 117(17): 2279 - 2287. [Abstract] [Full Text] [PDF]