The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies.
The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies.
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DOI：
10.1002/gepi.22161
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发表时间：
2018-12
影响因子：
2.1
通讯作者：
Chow CC
中科院分区：
文献类型：
--
作者：
Lee JJ;McGue M;Iacono WG;Chow CC
为了推断单核苷酸多态性（SNP）影响表型或与因果位点的连锁不平衡，我们必须保证任何SNP-表型相关性不是与同样影响该性状的环境变量混淆的结果。在本研究中，我们研究了连锁不平衡（LD）评分回归的特性，这是一种最近开发的方法，用于使用全基因组关联研究的汇总统计数据来确保混淆不会增加假阳性的数量。我们不把遗传变异的影响作为一个随机变量，因此能够得到关于这种方法的无偏性的结果。我们证明，LD评分回归可以在相当一般的条件下产生无偏或保守的零snp混淆估计。在亲本基因型通过某些环境机制影响后代表型的情况下，尽管LD评分与混杂程度之间的snp存在相关性，但这种稳健性仍然成立。此外，我们证明了LD评分回归可以产生合理可靠的遗传相关性估计，即使它对遗传协方差和两个单变量遗传力的估计有很大的偏差。
To infer that a single-nucleotide polymorphism (SNP) either affects a phenotype or is linkage disequilibrium with a causal site, we must have some assurance that any SNP-phenotype correlation is not the result of confounding with environmental variables that also affect the trait. In this study, we study the properties of linkage disequilibrium (LD) Score regression, a recently developed method for using summary statistics from genome-wide association studies to ensure that confounding does not inflate the number of false positives. We do not treat the effects of genetic variation as a random variable and thus are able to obtain results about the unbiasedness of this method. We demonstrate that LD Score regression can produce estimates of confounding at null SNPs that are unbiased or conservative under fairly general conditions. This robustness holds in the case of the parent genotype affecting the offspring phenotype through some environmental mechanism, despite the resulting correlation over SNPs between LD Scores and the degree of confounding. Additionally, we demonstrate that LD Score regression can produce reasonably robust estimates of the genetic correlation, even when its estimates of the genetic covariance and the two univariate heritabilities are substantially biased.
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影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
2.6
作者：
Beauchamp, Jonathan P.;Cesarini, David;Apicella, Coren
通讯作者：
Apicella, Coren
影响因子：
4.5
作者：
de Vlaming, Ronald;Okbay, Aysu;Koellinger, Philipp D.
通讯作者：
Koellinger, Philipp D.