US Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
Nat Genet. 2013 May;45(5):501-12. doi: 10.1038/ng.2606. Epub 2013 Apr 7.
Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
利用性状分布极值的方法可用于鉴定与常见性状相关的基因座，但这些基因座是否可推广到更广泛的人群尚不清楚。在一项针对体重指数、身高和腰臀比的第 5 百分位与第 95 百分位以及肥胖临床分类（包括多达 263407 名欧洲血统个体）的全基因组搜索中，我们在分布尾部发现了影响身高的 4 个新基因座（IGFBP4、H6PD、RSRC1 和 PPP2R2A），并发现了 7 个新基因座（HNF4G、RPTOR、GNAT2、MRPS33P4、ADCY9、HS6ST3 和 ZZZ3）可用于肥胖的临床分类。此外，我们发现基于极值和一般人群的性状之间的遗传结构和变异分布有很大的重叠，肥胖亚组之间的病因异质性很小。
