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Genetic variation and systemic lupus erythematosus: A field synopsis and systematic meta-analysis

 Dong Yeon Jeong  ;  Sang Woo Lee  ;  Young Ha Park  ;  Ji Hoon Choi  ;  Young Wook Kwon  ;  Gabin Moon  ;  Michael Eisenhut  ;  Andreas Kronbichler  ;  Jae Il Shin 
 AUTOIMMUNITY REVIEWS, Vol.17(6) : 553-566, 2018 
Journal Title
Issue Date
DNA Mutational Analysis/statistics & numerical data ; Genetic Predisposition to Disease ; Genome-Wide Association Study/statistics & numerical data ; Genotype ; Humans ; Systemic/epidemiology/*genetics Lupus Erythematosus ; Observational Studies as Topic/statistics & numerical data ; Genetic *Polymorphism ; Single Nucleotide Polymorphism
BFDP ; FPRP ; Gene variant ; Meta-analysis ; Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a multi-systemic severe autoimmune disease which results from the irreversible loss of self-tolerance and impaired molecular responses, especially an altered interferon signature. We synthesized all meta-analyses reporting a genetic association of SLE, and further investigated their validity to discover false positive results under Bayesian methods. We executed a PubMed search to extract the respective results regarding gene polymorphisms of SLE, published until June 30th 2017 and selected a single result per genetic variant among duplicates. Among 133 significant genotype comparisons, 45 (34%) were found noteworthy under both false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). From the meta-analysis of genome-wide association studies (GWAS), we could confirm that all significant comparisons were noteworthy under both Bayesian approaches. Both approaches may be advantageous for determining whether the reported associations are genuine, especially for interpreting results from observational studies instead of GWAS whose significance was determined in a more strict manner. When determining results from GWAS with a p-value ranging between 0.05 and 5x10(-8), other statistical approaches, rather than single standard significance may be beneficial. Taking into account these considerations, a proportion of meta-analyses claimed statistical significance, but these results need to be interpreted with caution.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
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