TY - JOUR
T1 - Strengthening Causal Inference for Complex Disease Using Molecular Quantitative Trait Loci
AU - Neumeyer, Sonja
AU - Hemani, Gibran
AU - Zeggini, Eleftheria
N1 - Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PY - 2019/11/9
Y1 - 2019/11/9
N2 - Large genome-wide association studies (GWAS) have identified loci that are associated with complex traits and diseases, but index variants are often not causal and reside in non-coding regions of the genome. To gain a better understanding of the relevant biological mechanisms, intermediate traits such as gene expression and protein levels are increasingly being investigated because these are likely mediators between genetic variants and disease outcome. Genetic variants associated with intermediate traits, termed molecular quantitative trait loci (molQTLs), can then be used as instrumental variables in a Mendelian randomization (MR) approach to identify the causal features and mechanisms of complex traits. Challenges such as pleiotropy and the non-specificity of molQTLs remain, and further approaches and methods need to be developed.
AB - Large genome-wide association studies (GWAS) have identified loci that are associated with complex traits and diseases, but index variants are often not causal and reside in non-coding regions of the genome. To gain a better understanding of the relevant biological mechanisms, intermediate traits such as gene expression and protein levels are increasingly being investigated because these are likely mediators between genetic variants and disease outcome. Genetic variants associated with intermediate traits, termed molecular quantitative trait loci (molQTLs), can then be used as instrumental variables in a Mendelian randomization (MR) approach to identify the causal features and mechanisms of complex traits. Challenges such as pleiotropy and the non-specificity of molQTLs remain, and further approaches and methods need to be developed.
U2 - 10.1016/j.molmed.2019.10.004
DO - 10.1016/j.molmed.2019.10.004
M3 - Review article (Academic Journal)
C2 - 31718940
SN - 1471-4914
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
ER -