Weedon Michael N, Frayling Timothy M
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, Magdalen Road, Exeter, EX1 2LU, UK.
Trends Genet. 2008 Dec;24(12):595-603. doi: 10.1016/j.tig.2008.09.006. Epub 2008 Oct 22.
Human height is a highly heritable, classic polygenic trait. Until recently, there had been limited success in identifying the specific genetic variants that explain normal variation of human height. The advent of large-scale genome-wide association studies, however, has led to dramatic progress. In the past 18 months, the first robust common variant associations were identified and there are now 44 loci known to influence normal variation of height. In this review, we summarize this exciting recent progress, discuss implicated biological pathways, the overlap with monogenic growth and skeletal dysplasia syndromes, links to disease and insights into the genetic architecture of this model polygenic trait. We also discuss the strong probability of finding several hundred more such loci in the near future.
人类身高是一种高度可遗传的经典多基因性状。直到最近,在识别解释人类身高正常变异的特定基因变异方面取得的成功有限。然而,大规模全基因组关联研究的出现带来了巨大进展。在过去的18个月里,首次发现了强有力的常见变异关联,目前已知有44个基因座会影响身高的正常变异。在这篇综述中,我们总结了这一近期令人兴奋的进展,讨论了涉及的生物学途径、与单基因生长和骨骼发育不良综合征的重叠、与疾病的联系以及对这种典型多基因性状遗传结构的见解。我们还讨论了在不久的将来发现数百个更多此类基因座的很大可能性。