Across diseases, meta-analyses are assumed to be one the major tools to achieve this [ 1- 4].
Transporter protein Gene Locus Function Significance for migraine Serotonin transporter, SERT SLC6A4 17q11.2 Reuptakes serotonin from the synapse, role in psychiatric disease Meta-analyses by the groups of Liu and Schurks report a positive association with SERT and migraine [27, 28].
This may explain the observed preventive effect of folic acid in the stroke trial meta-analysis and not in the ischaemic heart disease meta-analysis.
We then removed genes from the individual disease meta-analysis output gene list that were significantly differentially expressed from the three-disease meta-analysis (FDR ≤ 0.05), thereby omitting common differentially expressed genes in neurodegeneration from disease-specific gene lists.
10 studies were identified, with 517 504 individuals included in the coronary heart disease meta-analysis and 134 461 individuals in the cerebrovascular disease analysis.
One RCT was not included in the cardiovascular disease meta-analysis as it reported 0 patients experiencing chronic heart failure in both groups.
For invasive disease meta-analysis we only included publications reporting non- SIREVA data, considering that SIREVA data represent 96.7% of samples analyzed and would bias the pool estimation.
In advanced disease, meta-analyses have demonstrated that the presence of a BRAF mutation is independently associated with a worse survival outcome [97 99].
The resulting individual disease meta-analysis gene list was then input into GSEA PreRank for assessment of GO term enrichment as described earlier.
In order to find whether a common trend exists amongst the current literature for the effect of years since drinking cessation on risk of disease, meta-analysis in the form of a Generalised Least Squares model (GLS) was utilised [ 22].
Search terms included the expanded medical subject heading (MESH) of cardiovascular disease, meta-analysis as a MESH topic or publication type, and then the four individual risk markers as either the MESH term or text words.
