MR-PheWAS: hypothesis prioritization among potential causal effects of body mass index on many outcomes, using Mendelian randomization.

Sci Rep 2015 Nov 16;5:16645. Epub 2015 Nov 16.

MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol.

Observational cohort studies can provide rich datasets with a diverse range of phenotypic variables. However, hypothesis-driven epidemiological analyses by definition only test particular hypotheses chosen by researchers. Furthermore, observational analyses may not provide robust evidence of causality, as they are susceptible to confounding, reverse causation and measurement error. Using body mass index (BMI) as an exemplar, we demonstrate a novel extension to the phenome-wide association study (pheWAS) approach, using automated screening with genotypic instruments to screen for causal associations amongst any number of phenotypic outcomes. We used a sample of 8,121 children from the ALSPAC dataset, and tested the linear association of a BMI-associated allele score with 172 phenotypic outcomes (with variable sample sizes). We also performed an instrumental variable analysis to estimate the causal effect of BMI on each phenotype. We found 21 of the 172 outcomes were associated with the allele score at an unadjusted pā€‰<ā€‰0.05 threshold, and use Bonferroni corrections, permutation testing and estimates of the false discovery rate to consider the strength of results given the number of tests performed. The most strongly associated outcomes included leptin, lipid profile, and blood pressure. We also found novel evidence of effects of BMI on a global self-worth score.

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http://dx.doi.org/10.1038/srep16645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644974PMC
November 2015
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References

(Supplied by CrossRef)

LR Cardon et al.
Nature Reviews Genetics 2001

HM Colhoun et al.
Lancet 2003

MI McCarthy et al.
Nature reviews. Genetics 2008

LA Hindorff et al.
P Natl Acad Sci USA 2009

G Davey Smith et al.
International journal of epidemiology 2001

G Davey Smith et al.
Plos Med 2007

G Davey Smith et al.
Brit Med J 2002

G Davey Smith et al.
International journal of epidemiology 2003

G Davey Smith et al.
Human molecular genetics 2014

G Davey Smith et al.
Genes Nutr 2011

V Didelez et al.
Stat Methods Med Res 2007

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