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.
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.
Authors: Y-F Chiu; L-M Chuang; H-Y Kao; K-C Shih; M-W Lin; W-J Lee; T Quertermous; J D Curb; I Chen; B L Rodriguez; C A Hsiung Journal: Hum Genet Date: 2010-08-20 Impact factor: 4.132
Authors: David Karasik; Yanhua Zhou; L Adrienne Cupples; Marian T Hannan; Douglas P Kiel; Serkalem Demissie Journal: J Bone Miner Res Date: 2009-04 Impact factor: 6.741
Authors: David Karasik; M Carola Zillikens; Yi-Hsiang Hsu; Ali Aghdassi; Kristina Akesson; Najaf Amin; Inês Barroso; David A Bennett; Lars Bertram; Murielle Bochud; Ingrid B Borecki; Linda Broer; Aron S Buchman; Liisa Byberg; Harry Campbell; Natalia Campos-Obando; Jane A Cauley; Peggy M Cawthon; John C Chambers; Zhao Chen; Nam H Cho; Hyung Jin Choi; Wen-Chi Chou; Steven R Cummings; Lisette C P G M de Groot; Phillip L De Jager; Ilja Demuth; Luda Diatchenko; Michael J Econs; Gudny Eiriksdottir; Anke W Enneman; Joel Eriksson; Johan G Eriksson; Karol Estrada; Daniel S Evans; Mary F Feitosa; Mao Fu; Christian Gieger; Harald Grallert; Vilmundur Gudnason; Launer J Lenore; Caroline Hayward; Albert Hofman; Georg Homuth; Kim M Huffman; Lise B Husted; Thomas Illig; Erik Ingelsson; Till Ittermann; John-Olov Jansson; Toby Johnson; Reiner Biffar; Joanne M Jordan; Antti Jula; Magnus Karlsson; Kay-Tee Khaw; Tuomas O Kilpeläinen; Norman Klopp; Jacqueline S L Kloth; Daniel L Koller; Jaspal S Kooner; William E Kraus; Stephen Kritchevsky; Zoltán Kutalik; Teemu Kuulasmaa; Johanna Kuusisto; Markku Laakso; Jari Lahti; Thomas Lang; Bente L Langdahl; Markus M Lerch; Joshua R Lewis; Christina Lill; Lars Lind; Cecilia Lindgren; Yongmei Liu; Gregory Livshits; Östen Ljunggren; Ruth J F Loos; Mattias Lorentzon; Jian'an Luan; Robert N Luben; Ida Malkin; Fiona E McGuigan; Carolina Medina-Gomez; Thomas Meitinger; Håkan Melhus; Dan Mellström; Karl Michaëlsson; Braxton D Mitchell; Andrew P Morris; Leif Mosekilde; Maria Nethander; Anne B Newman; Jeffery R O'Connell; Ben A Oostra; Eric S Orwoll; Aarno Palotie; Munro Peacock; Markus Perola; Annette Peters; Richard L Prince; Bruce M Psaty; Katri Räikkönen; Stuart H Ralston; Samuli Ripatti; Fernando Rivadeneira; John A Robbins; Jerome I Rotter; Igor Rudan; Veikko Salomaa; Suzanne Satterfield; Sabine Schipf; Chan Soo Shin; Albert V Smith; Shad B Smith; Nicole Soranzo; Timothy D Spector; Alena Stancáková; Kari Stefansson; Elisabeth Steinhagen-Thiessen; Lisette Stolk; Elizabeth A Streeten; Unnur Styrkarsdottir; Karin M A Swart; Patricia Thompson; Cynthia A Thomson; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Emmi Tikkanen; Gregory J Tranah; André G Uitterlinden; Cornelia M van Duijn; Natasja M van Schoor; Liesbeth Vandenput; Peter Vollenweider; Henry Völzke; Jean Wactawski-Wende; Mark Walker; Nicholas J Wareham; Dawn Waterworth; Michael N Weedon; H-Erich Wichmann; Elisabeth Widen; Frances M K Williams; James F Wilson; Nicole C Wright; Laura M Yerges-Armstrong; Lei Yu; Weihua Zhang; Jing Hua Zhao; Yanhua Zhou; Carrie M Nielson; Tamara B Harris; Serkalem Demissie; Douglas P Kiel; Claes Ohlsson Journal: Am J Clin Nutr Date: 2019-02-01 Impact factor: 7.045