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, Jaeil Shin

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

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 5 × 10 −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.

Original languageEnglish
Pages (from-to)553-566
Number of pages14
JournalAutoimmunity Reviews
Volume17
Issue number6
DOIs
Publication statusPublished - 2018 Jun 1

Fingerprint

Genome-Wide Association Study
Systemic Lupus Erythematosus
Meta-Analysis
Bayes Theorem
Self Tolerance
PubMed
Interferons
Autoimmune Diseases
Observational Studies
Genotype
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Jeong, Dong Yeon ; Lee, Sang Woo ; Park, Young Ha ; Choi, Ji Hoon ; Kwon, Young Wook ; Moon, Gabin ; Eisenhut, Michael ; Kronbichler, Andreas ; Shin, Jaeil. / Genetic variation and systemic lupus erythematosus : A field synopsis and systematic meta-analysis. In: Autoimmunity Reviews. 2018 ; Vol. 17, No. 6. pp. 553-566.
@article{8bc4fce73f16484fb5c078b5bfde8ffa,
title = "Genetic variation and systemic lupus erythematosus: A field synopsis and systematic meta-analysis",
abstract = "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 5 × 10 −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.",
author = "Jeong, {Dong Yeon} and Lee, {Sang Woo} and Park, {Young Ha} and Choi, {Ji Hoon} and Kwon, {Young Wook} and Gabin Moon and Michael Eisenhut and Andreas Kronbichler and Jaeil Shin",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.autrev.2017.12.011",
language = "English",
volume = "17",
pages = "553--566",
journal = "Autoimmunity Reviews",
issn = "1568-9972",
publisher = "Elsevier",
number = "6",

}

Jeong, DY, Lee, SW, Park, YH, Choi, JH, Kwon, YW, Moon, G, Eisenhut, M, Kronbichler, A & Shin, J 2018, 'Genetic variation and systemic lupus erythematosus: A field synopsis and systematic meta-analysis', Autoimmunity Reviews, vol. 17, no. 6, pp. 553-566. https://doi.org/10.1016/j.autrev.2017.12.011

Genetic variation and systemic lupus erythematosus : A field synopsis and systematic meta-analysis. / Jeong, Dong Yeon; Lee, Sang Woo; Park, Young Ha; Choi, Ji Hoon; Kwon, Young Wook; Moon, Gabin; Eisenhut, Michael; Kronbichler, Andreas; Shin, Jaeil.

In: Autoimmunity Reviews, Vol. 17, No. 6, 01.06.2018, p. 553-566.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Genetic variation and systemic lupus erythematosus

T2 - A field synopsis and systematic meta-analysis

AU - Jeong, Dong Yeon

AU - Lee, Sang Woo

AU - Park, Young Ha

AU - Choi, Ji Hoon

AU - Kwon, Young Wook

AU - Moon, Gabin

AU - Eisenhut, Michael

AU - Kronbichler, Andreas

AU - Shin, Jaeil

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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 5 × 10 −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.

AB - 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 5 × 10 −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.

UR - http://www.scopus.com/inward/record.url?scp=85046634591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046634591&partnerID=8YFLogxK

U2 - 10.1016/j.autrev.2017.12.011

DO - 10.1016/j.autrev.2017.12.011

M3 - Review article

VL - 17

SP - 553

EP - 566

JO - Autoimmunity Reviews

JF - Autoimmunity Reviews

SN - 1568-9972

IS - 6

ER -