Combining evidence from Mendelian randomization and colocalization: Review and comparison of approaches.
Combining evidence from Mendelian randomization and colocalization: Review and comparison of approaches.
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DOI：
10.1016/j.ajhg.2022.04.001
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发表时间：
2022-05-05
影响因子：
9.8
通讯作者：
Burgess S
中科院分区：
文献类型：
--
作者：
Zuber V;Grinberg NF;Gill D;Manipur I;Slob EAW;Patel A;Wallace C;Burgess S
孟德尔随机化和共定位是两种统计方法，可用于全基因组关联研究（GWASs）的汇总数据，以了解性状与疾病之间的关系。然而，尽管它们的范围相似，但它们的目标、实施和解释不同，部分原因是它们是为不同的科学界开发的。孟德尔随机化评估暴露的遗传预测因子是否与结果相关，并将关联解释为暴露对结果有因果影响的证据，而共定位评估两个特征是否受到相同或不同的因果变异的影响。当考虑单个遗传区域的遗传变异时，这两种方法都可以执行。虽然积极的共定位发现通常意味着非零孟德尔随机化估计，但反过来并不普遍成立：有几种情况会导致非零孟德尔随机化估计，但缺乏共定位的证据。其中包括暴露和结果之间存在明显但相关的因果变量，这违反了孟德尔随机化假设，并且与结果缺乏强烈的关联。由于同地定位是在GWAS传统中发展起来的，通常只有在有强有力的证据表明同地定位与两种特征有关时，才会得出结论。相比之下，从孟德尔随机化可以得到一个非零的估计，尽管只有名义上显著的遗传关联与结果在位点。在这篇综述中，我们讨论了这两种方法如何为潜在的治疗靶点提供补充信息。
Mendelian randomization and colocalization are two statistical approaches that can be applied to summarized data from genome-wide association studies (GWASs) to understand relationships between traits and diseases. However, despite similarities in scope, they are different in their objectives, implementation, and interpretation, in part because they were developed to serve different scientific communities. Mendelian randomization assesses whether genetic predictors of an exposure are associated with the outcome and interprets an association as evidence that the exposure has a causal effect on the outcome, whereas colocalization assesses whether two traits are affected by the same or distinct causal variants. When considering genetic variants in a single genetic region, both approaches can be performed. While a positive colocalization finding typically implies a non-zero Mendelian randomization estimate, the reverse is not generally true: there are several scenarios which would lead to a non-zero Mendelian randomization estimate but lack evidence for colocalization. These include the existence of distinct but correlated causal variants for the exposure and outcome, which would violate the Mendelian randomization assumptions, and a lack of strong associations with the outcome. As colocalization was developed in the GWAS tradition, typically evidence for colocalization is concluded only when there is strong evidence for associations with both traits. In contrast, a non-zero estimate from Mendelian randomization can be obtained despite only nominally significant genetic associations with the outcome at the locus. In this review, we discuss how the two approaches can provide complementary information on potential therapeutic targets.
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影响因子：
4.5
作者：
Baird DA;Liu JZ;Zheng J;Sieberts SK;Perumal T;Elsworth B;Richardson TG;Chen CY;Carrasquillo MM;Allen M;Reddy JS;De Jager PL;Ertekin-Taner N;Mangravite LM;Logsdon B;Estrada K;Haycock PC;Hemani G;Runz H;Smith GD;Gaunt TR;AMP-AD eQTL working group
通讯作者：
AMP-AD eQTL working group
DOI：
10.1136/bmj.j1648
发表时间：
2017-04-24
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Benn M;Nordestgaard BG;Frikke-Schmidt R;Tybjærg-Hansen A
通讯作者：
Tybjærg-Hansen A
DOI：
10.1097/ede.0000000000000161
发表时间：
2014-11
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Burgess S;Davies NM;Thompson SG;EPIC-InterAct Consortium
通讯作者：
EPIC-InterAct Consortium
影响因子：
64.5
作者：
Astle, William J.;Elding, Heather;Soranzo, Nicole
通讯作者：
Soranzo, Nicole
影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.