Genome partitioning of genetic variation for complex traits using common SNPs.
Genome partitioning of genetic variation for complex traits using common SNPs.
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作者：
最近，我们报道了一种方法来估计表型方差的比例解释的所有SNP全基因组关联研究，并估计，人类身高的遗传力的一半是由常见的SNP捕获。在这里，我们将身高，体重指数（BMI），血管性血友病因子（vWF）和QT间期（QTi）的遗传变异划分到染色体和染色体片段上，使用586，898个SNP对11，586个无关个体进行基因分型。我们估计身高、BMI、vWF和QTi的变异分别约为45%、17%、25%和21%，可以通过同时考虑所有常染色体SNP来解释，身高、BMI和vWF的X染色体SNP进一步解释约为0.5-1%。我们发现，解释每个染色体的高度和QTi的方差是成比例的染色体上的总基因长度。在全基因组分析中，基因内或附近的常见SNP比基因间的SNP解释更多的变异。我们提出了一种新的方法来估计由于神秘的相关性和人口分层的变化。我们的结果提供了进一步的证据，证明遗传力的很大一部分是由与常见SNP连锁不平衡的因果变异造成的;身高、BMI和QTi是高度多基因性状;并且由部分基因组解释的加性变异与其中基因内所含DNA的总长度大致成比例。
Recently, we reported a method to estimate the proportion of phenotypic variance explained by all SNPs from genome-wide association studies, and estimated that half of the heritability for human height was captured by common SNPs. Here we partition genetic variation for height, body mass index (BMI), von Willebrand factor (vWF) and QT interval (QTi) onto chromosomes and chromosome segments, using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ~45%, ~17%, ~25% and ~21% of variance in height, BMI, vWF and QTi, respectively, can be explained by considering all autosomal SNPs simultaneously, and a further ~0.5–1% by X-chromosome SNPs for height, BMI and vWF. We show that variance explained by each chromosome for height and QTi is proportional to the total gene length on that chromosome. In genome-wide analyses, common SNPs in or near genes explain more variation than SNPs between genes. We propose a novel approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is accounted for by causal variants in linkage disequilibrium with common SNPs; that height, BMI and QTi are highly polygenic traits; and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein.
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DOI：
10.1073/pnas.0906182107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Eyre-Walker, Adam
通讯作者：
Eyre-Walker, Adam
影响因子：
9.8
作者：
Liu, Jimmy Z.;Mcrae, Allan F.;Macgregor, Stuart
通讯作者：
Macgregor, Stuart
影响因子：
168.9
作者：
RIMM, EB;GIOVANNUCCI, EL;STAMPFER, MJ
通讯作者：
STAMPFER, MJ
DOI：
10.1161/circgenetics.108.829747
发表时间：
2009-02
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Psaty BM;O'Donnell CJ;Gudnason V;Lunetta KL;Folsom AR;Rotter JI;Uitterlinden AG;Harris TB;Witteman JC;Boerwinkle E;CHARGE Consortium
通讯作者：
CHARGE Consortium
稀有变体会产生整个基因组的关联。
影响因子：
9.8
作者：
Dickson SP;Wang K;Krantz I;Hakonarson H;Goldstein DB
通讯作者：
Goldstein DB