PT  - JOURNAL ARTICLE
AU  - Gibran Hemani
AU  - Jie Zheng
AU  - Kaitlin H Wade
AU  - Charles Laurin
AU  - Benjamin Elsworth
AU  - Stephen Burgess
AU  - Jack Bowden
AU  - Ryan Langdon
AU  - Vanessa Tan
AU  - James Yarmolinsky
AU  - Hashem A. Shihab
AU  - Nicholas Timpson
AU  - David M Evans
AU  - Caroline Relton
AU  - Richard M Martin
AU  - George Davey Smith
AU  - Tom R Gaunt
AU  - Philip C Haycock
ED  - Soranzo, Nicole
ED  - van Heel, David A
ED  - Okada, Yukinori
ED  - Tang, Clara S.
ED  - Garcia-Barcelo, Merce
ED  - Tam, Paul KH
ED  - Jacobsen, Kaya Kvarme
ED  - Jones, Gregory T
ED  - Bown, Matthew J
ED  - Albagha, Omar
ED  - Ralston, Stuart H.
ED  - Franke, Andre
ED  - Fischer, Annegret
ED  - Ellinghaus, David
ED  - Försti, Asta
ED  - Thomsen, Hauke
ED  - Landi, Stefano
ED  - Cordell, Heather
ED  - Manichaikul, Ani W
ED  - Barr, R Graham
ED  - Lee, Jeffrey E
TI  - MR-Base: a platform for systematic causal inference across the phenome using billions of genetic associations
AID  - 10.1101/078972
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 078972
4099  - http://biorxiv.org/content/early/2016/12/16/078972.short
4100  - http://biorxiv.org/content/early/2016/12/16/078972.full
AB  - Published genetic associations can be used to infer causal relationships between phenotypes, bypassing the need for individual-level genotype or phenotype data. We have curated complete summary data from 1094 genome-wide association studies (GWAS) on diseases and other complex traits into a centralised database, and developed an analytical platform that uses these data to perform Mendelian randomization (MR) tests and sensitivity analyses (MR-Base, http://www.mrbase.org). Combined with curated data of published GWAS hits for phenomic measures, the MR-Base platform enables millions of potential causal relationships to be evaluated. We use the platform to predict the impact of lipid lowering on human health. While our analysis provides evidence that reducing LDL-cholesterol, lipoprotein(a) or triglyceride levels reduce coronary disease risk, it also suggests causal effects on a number of other non-vascular outcomes, indicating potential for adverse-effects or drug repositioning of lipid-lowering therapies.