Using multiple genetic variants as instrumental variables for modifiable risk factors

Palmer, Tom; Lawlor, Debbie A.; Harbord, Roger; Sheehan, Nuala A.; Tobias, Jonathan H.; Timpson, Nicholas J.; Smith, George Davey; Sterne, Jonathan A C

doi:10.1177/0962280210394459

articleStatistical Methods in Medical ResearchJan 7, 2011GREEN OA

Using multiple genetic variants as instrumental variables for modifiable risk factors

TPTom Palmer DADebbie A. Lawlor RHRoger Harbord NANuala A. Sheehan JHJonathan H. Tobias

University of Bristol · University of Leicester

PubMed

Indexed incrossrefpubmed

Abstract

Mendelian randomisation analyses use genetic variants as instrumental variables (IVs) to estimate causal effects of modifiable risk factors on disease outcomes. Genetic variants typically explain a small proportion of the variability in risk factors; hence Mendelian randomisation analyses can require large sample sizes. However, an increasing number of genetic variants have been found to be robustly associated with disease-related outcomes in genome-wide association studies. Use of multiple instruments can improve the precision of IV estimates, and also permit examination of underlying IV assumptions. We discuss the use of multiple genetic variants in Mendelian randomisation analyses with continuous outcome…

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Topics

Keywords

Mendelian randomization
Instrumental variable
Statistics
Sample size determination
Genetic association
Mendelian inheritance
Genome-wide association study
Econometrics

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