Genome-wide Gene and Pathway Analysis
Overview
Affiliations
Current GWAS have primarily focused on testing association of single SNPs. To only test for association of single SNPs has limited utility and is insufficient to dissect the complex genetic structure of many common diseases. To meet conceptual and technical challenges raised by GWAS, we suggest gene and pathway-based GWAS as complementary to the current single SNP-based GWAS. This publication develops three statistics for testing association of genes and pathways with disease: linear combination test, quadratic test and decorrelation test, which take correlations among SNPs within a gene or genes within a pathway into account. The null distribution of the suggested statistics is examined and the statistics are applied to GWAS of rheumatoid arthritis in the Wellcome Trust Case-Control Consortium and the North American Rheumatoid Arthritis Consortium studies. The preliminary results show that the suggested gene and pathway-based GWAS offer several remarkable features. First, not only can they identify the genes that have large genetic effects, but also they can detect new genes in which each single SNP conferred a small amount of disease risk, and their joint actions can be implicated in the development of diseases. Second, gene and pathway-based analysis can allow the formation of the core of pathway definition of complex diseases and unravel the functional bases of an association finding. Third, replication of association findings at the gene or pathway level is much easier than replication at the individual SNP level.
Identification of a Predictive Model for Schizophrenia Based on SNPs in a Chinese Population.
Yang Z, Yao S, Xu Y, Zhang X, Shi Y, Wang L Neuropsychiatr Dis Treat. 2024; 20:1553-1561.
PMID: 39139656 PMC: 11321330. DOI: 10.2147/NDT.S466554.
Lee S, Yang H, Lee H, Park D, Kong S, Park S Front Genet. 2022; 13:928783.
PMID: 36081994 PMC: 9446437. DOI: 10.3389/fgene.2022.928783.
Using common genetic variants to find drugs for common epilepsies.
Mirza N, Stevelink R, Taweel B, Koeleman B, Marson A Brain Commun. 2022; 3(4):fcab287.
PMID: 34988442 PMC: 8710935. DOI: 10.1093/braincomms/fcab287.
Metagenomics and chemotherapy-induced nausea: A roadmap for future research.
Crowder S, Hoogland A, Welniak T, LaFranchise E, Carpenter K, Li D Cancer. 2021; 128(3):461-470.
PMID: 34643945 PMC: 8776572. DOI: 10.1002/cncr.33892.
Eskandari S, Sajadimajd S, Alaei L, Soheilikhah Z, Derakhshankhah H, Bahrami G Neurotox Res. 2021; 39(5):1589-1612.
PMID: 34169405 DOI: 10.1007/s12640-021-00381-7.