Two data sources were included in the meta-analysis: (i) studies that looked at the effect of the variant on traits of interest by genotyping the variant; and (ii) look-up from GWAS of traits of interest.

Studies were sourced through Medline, Embase, HuGe Navigator, Web of Science, bioRxiv and medRxiv. The search terms used were: ‘(MBOAT7 or membrane-bound-o-acyltransferase) or (rs641738 or rs626283) or (TMC4)’. In addition, HuGe Navigator Phenopedia was searched using terms related to liver disease (see Supplementary Methods). There were no restrictions on either date or language. The search was completed on July 28, 2020. Reference lists of publications were also reviewed.

A separate search was conducted for all potentially relevant GWAS through GWAS Catalogue,25 Phenoscanner,26 Type 2 diabetes knowledge portal27 and Cardiovascular disease knowledge portal28 (see Supplementary Methods).

After removal of duplicates, titles and abstracts were screened for eligibility independently by 2 authors (investigators), with inclusion/exclusion criteria applied to potentially eligible full texts.

HuGENet guidelines29 were followed throughout and MOOSE reporting guidelines30 were used. This study was prospectively registered on the PROSPERO Database of Systematic Reviews (CRD42018105507; www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018105507).

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