NDLI: Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets

Content Provider	Springer Nature Link
Author	Saeed, Mohammad
Copyright Year	2017
Abstract	Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.
Starting Page	295
Ending Page	302
Page Count	8
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	69
Issue Number	5
e-ISSN	14321211
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-02-28
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Lupus Linkage disequilibrium Genome-wide association study Gene-based tests Meta-analysis Immunology Human Genetics Gene Function Cell Biology Allergology
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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