生物谷报道:一项考查人数超过35000人、覆盖整个人类基因组的研究表明,与骨关节炎相关的常见遗传突变在人体身高上起着重要的作用。此项研究1月13日刊登在《自然—遗传学》(Nature Genetics)上。研究小组部分成员来自美国国立卫生研究院。
在此项最新的基因组范围内的扫描中,与身高最为相关的基因突变是人类基因组的一个特定区域,该区域被认为是影响着生长分化因子5(growth differentiation factor 5;GDF5)基因的表达。GDF5参与调控腿骨和其他长骨的软骨发育。很少有GDF5基因的突变体表明它与骨骼发育相关,越来越多的突变体将该基因的常见突变体与臀部、膝盖的骨关节炎(osteoarthritis)的易感性联系起来。
“我们研究的人类常见突变体中主要有两个明显特征,一是身材短小,二是像之前所述的那样,具有较高的骨关节炎的发病率。” 此项研究的通讯作者Karen L. Mohlke介绍说,她是北卡罗来纳大学教堂山分校的教授,“我们的研究暗示着在遗传导致的身高缺陷与骨关节炎之间,骨生长和发育起着重要的作用。”
Mohlke和她的同事强调说,新的研究仅仅涉及到部分影响身高的遗传基因,这表明要对身高这一复杂的人类性状进行完整的描述仍需更多更深入的研究。
许多因子都影响着人体的身高,包括遗传、产前环境、饮食等。当前,科学家认为影响人类身高的多样性中,将近80%来自于遗传。但是,这个最新的遗传突变体,以及另外一个最新发现的与身高相关的遗传突变体HMGA2,两者对人体身高的影响之和仍不到1%。
“很多遗传突变对身高的影响都很小,所以需要采集更大量的数据才能真正找出这些基因。”美国国立人类基因组研究所(National Human Genome Research Institute;NHGRI)的主任Francis S. Collins介绍说,他是此项研究的共同作者。(来源:生命经纬)
生物谷推荐原始出处:
Nature Genetics
Published online: 13 January 2008 | doi:10.1038/ng.74
Common variants in the GDF5-UQCC region are associated with variation in human height
Serena Sanna1,2,19, Anne U Jackson1,19, Ramaiah Nagaraja3, Cristen J Willer1, Wei-Min Chen1,4, Lori L Bonnycastle5, Haiqing Shen6, Nicholas Timpson7,8, Guillaume Lettre9, Gianluca Usala2, Peter S Chines5, Heather M Stringham1, Laura J Scott1, Mariano Dei2, Sandra Lai2, Giuseppe Albai2, Laura Crisponi2, Silvia Naitza2, Kimberly F Doheny10, Elizabeth W Pugh10, Yoav Ben-Shlomo7, Shah Ebrahim11, Debbie A Lawlor7,8, Richard N Bergman12, Richard M Watanabe12,13, Manuela Uda2, Jaakko Tuomilehto14, Josef Coresh15, Joel N Hirschhorn9, Alan R Shuldiner6,16, David Schlessinger3, Francis S Collins5, George Davey Smith7,8, Eric Boerwinkle17, Antonio Cao2, Michael Boehnke1, Gonçalo R Abecasis1 & Karen L Mohlke18
Identifying genetic variants that influence human height will advance our understanding of skeletal growth and development. Several rare genetic variants have been convincingly and reproducibly associated with height in mendelian syndromes, and common variants in the transcription factor gene HMGA2 are associated with variation in height in the general population1. Here we report genome-wide association analyses, using genotyped and imputed markers, of 6,669 individuals from Finland and Sardinia, and follow-up analyses in an additional 28,801 individuals. We show that common variants in the osteoarthritis-associated locus2GDF5-UQCC contribute to variation in height with an estimated additive effect of 0.44 cm (overall P < 10-15). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development.
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy.
Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 21224, USA.
Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Department of Social Medicine, University of Bristol, Canynge Hall, Bristol BS8 2PR, UK.
Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Canynge Hall, Bristol BS8 2PR, UK.
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA.
Center for Inherited Disease Research (CIDR), Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA.
London School of Hygiene and Tropical Medicine, University of London, London WC1E 7HT, UK.
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, 00300 Helsinki, and Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
Welch Center for Prevention, Epidemiology and Clinical Research, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Geriatric Research and Education Center, Veterans Administration Medical Center, Baltimore, Maryland 21201, USA.
Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77225, USA.
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
These authors contributed equally to this work.
Correspondence to: Karen L Mohlke18 e-mail: mohlke@med.unc.edu
Correspondence to: Gonçalo R Abecasis1 e-mail: goncalo@umich.edu