Locus and gene-based GWAS meta-analysis identifies new diabetic nephropathy genes

• Published in: Immunogenetics (New York) Vol. 70; no. 6; pp. 347 - 353
• Main Author: Saeed, Mohammad
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2018; Springer Nature B.V
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Clustering; Datasets; Diabetes; Diabetes mellitus; Diabetic nephropathy; Gene Function; Genes; Genome-wide association studies; Genomes; Human Genetics; Immunology; Inositol polyphosphate 5-phosphatase; Loci; Meta-analysis; Nephropathy; Netrin-1; Original Article; Single-nucleotide polymorphism; Locus-based test; Gene-based test; Diabetic nephropathy; Genome-wide association study
• ISSN: 0093-7711; 1432-1211; 1432-1211
• DOI: 10.1007/s00251-017-1044-0

Objective Assimilation of SNPs Interacting in Synchrony (OASIS) is a locus-based clustering algorithm recently described that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders. Diabetic nephropathy (DN) is incompletely understood due to a paucity of genes identified despite several GWAS. OASIS was applied to three DN dbGAP GWAS datasets (4725 subjects; 1.06 million SNPs). OASIS identified 19 DN genes which were verified using single variant replication in a standard association study and gene-based analysis using GATES. CARS and FRMD3 were confirmed as DN genes, and five known diabetes-associated genes, viz. NLRP3 , INPPL1 , PIK3C2G , NRXN3 , and TBC1D4 , not previously identified using these datasets were discovered. Furthermore, three additional novel DN genes were found which replicated in two sets of analysis, viz. NTN1 , EBF2 , and DNAH11 . Hence, composite analysis with OASIS, gene-based, and single variant association testing can be universally applied to existing GWAS datasets for the identification of new genes.