Linkage of genes to total lean body mass in normal women

Gregory Livshits, Scott G. Wilson, Tim D. Spector

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3171-3176
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number8
DOIs
Publication statusPublished - 1 Jan 2007
Externally publishedYes

Fingerprint

Dizygotic Twins
Genes
Fats
X-Rays
Genome
Body Weights and Measures
Chromosomes, Human, Pair 14
Bone and Bones
Chromosomes, Human, Pair 12
Body Height
Quantitative Trait Loci
Chromosomes
Analysis of Variance
Bone
Body Weight
X rays
Research
Deterioration
United Kingdom

Cite this

Livshits, Gregory ; Wilson, Scott G. ; Spector, Tim D. / Linkage of genes to total lean body mass in normal women. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 8. pp. 3171-3176.
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abstract = "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.",
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Linkage of genes to total lean body mass in normal women. / Livshits, Gregory; Wilson, Scott G.; Spector, Tim D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 8, 01.01.2007, p. 3171-3176.

Research output: Contribution to journalArticle

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N2 - 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.

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