Projects per year
Abstract
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 p<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.
Original language | English |
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Article number | 16645 |
Number of pages | 17 |
Journal | Scientific Reports |
Volume | 5 |
DOIs | |
Publication status | Published - 16 Nov 2015 |
Research Groups and Themes
- Jean Golding
Fingerprint
Dive into the research topics of 'MR-PheWAS: Hypothesis prioritization among potential causal effects of body mass index on many outcomes, using Mendelian randomization'. Together they form a unique fingerprint.Projects
- 4 Finished
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MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
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MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
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IEU Theme 2
Flach, P. A. (Principal Investigator), Gaunt, T. R. (Principal Investigator) & Gaunt, T. R. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
Profiles
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Dr Louise A C Millard
- Bristol Medical School (PHS) - Senior Lecturer in Health Data Science (Co-Director MSc in Medical Statistics and Health Data Scienc
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
Person: Academic , Member