Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus

Arthritis Research & Therapy
Antonio JuliàAntonio Fernández-Nebro

Abstract

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10- 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis...Continue Reading

References

Nov 1, 1982·Arthritis and Rheumatism·E M TanR J Winchester
Jan 7, 2003·Nature Immunology·Erin JanssenWeiguo Zhang
Jul 6, 2004·Nature Cell Biology·Ryuji HamamotoYusuke Nakamura
Jun 19, 2007·Nature Genetics·Jonathan MarchiniPeter Donnelly
Jan 22, 2008·Nature Genetics·UNKNOWN International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN)Jennifer A Kelly
Jan 24, 2009·Nature Genetics·Robert R GrahamPatrick M Gaffney
Jan 16, 2010·American Journal of Human Genetics·Rita M CantorJanet S Sinsheimer
Jul 10, 2010·Bioinformatics·Cristen J WillerGonçalo R Abecasis
Aug 12, 2010·Annals of the Rheumatic Diseases·Casandra C van BavelJohan van der Vlag
Oct 29, 2010·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Mar 2, 2012·Nature Reviews. Cancer·Serena S KwekLawrence Fong
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Dec 28, 2012·Nature Methods·Olivier DelaneauJonathan Marchini
Jul 23, 2013·Nature Reviews. Drug Discovery·Robert M PlengeDavid Altshuler
Sep 17, 2013·Nature·Tuuli LappalainenEmmanouil T Dermitzakis
Sep 27, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew L RankinJohn Douhan
Nov 19, 2013·Nucleic Acids Research·David CroftPeter D'Eustachio
Jan 7, 2014·Nature·Yukinori OkadaRobert M Plenge
Jan 13, 2015·Nature Genetics·Rudolf S N FehrmannLude Franke
Feb 20, 2015·Nature·Casey E RomanoskiGenevieve Almouzni
May 21, 2015·Annals of the Rheumatic Diseases·Antonio JuliàSara Marsal
Jun 30, 2015·Nature Genetics·Matthew R NelsonPhilippe Sanseau
Oct 18, 2015·Nucleic Acids Research·Minoru KanehisaMao Tanabe
Jan 9, 2016·The Journal of Investigative Dermatology·Adrià AteridoSara Marsal
Jan 26, 2016·PLoS Computational Biology·David LamparterSven Bergmann
Feb 16, 2016·Expert Opinion on Investigational Drugs·Victor R Pimentel-QuirozGraciela S Alarcón
Nov 5, 2016·European Journal of Immunology·Michael Reth, Michael R Gold
Nov 23, 2016·Nature Reviews. Rheumatology·George C TsokosKathleen E Sullivan
Jul 8, 2017·American Journal of Human Genetics·Peter M VisscherJian Yang
Jan 24, 2018·Nature Communications·Sílvia Bonàs-GuarchDavid Torrents

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Citations

Dec 13, 2018·Current Opinion in Rheumatology·Eva SchrezenmeierThomas Dörner
May 24, 2019·Immunotherapy·Chrysoula StathopoulouGeorge Bertsias
Jul 14, 2019·Lupus·M F Ugarte-GilG S Alarcón
Dec 2, 2018·Frontiers in Endocrinology·Hui LiuDongfeng Zhang
Jul 19, 2019·Scientific Reports·Meifeng XuShengxiang Xiao
Aug 23, 2019·Current Opinion in Rheumatology·Nina OparinaMarta E Alarcón-Riquelme
May 19, 2020·Human Molecular Genetics·James DingGisela Orozco
Dec 20, 2020·Nature Reviews. Rheumatology·Simon FillatreauThomas Dörner
May 5, 2021·Journal of the American Society of Nephrology : JASN·Atlas KhanKrzysztof Kiryluk
Jun 25, 2020·Arthritis Research & Therapy·Samaneh MalekniaKaveh Kavousi
Jul 4, 2021·Rheumatic Diseases Clinics of North America·Susan P Canny, Shaun W Jackson
Jul 25, 2021·International Journal of Molecular Sciences·Mohammad SaeedChary López-Pedrera
Sep 30, 2021·Molecular Genetics & Genomic Medicine·Jiahao ChenDongfeng Zhang
Nov 4, 2021·Seminars in Immunopathology·Eunji HaKwangwoo Kim
Nov 23, 2021·Frontiers in Immunology·Xingang LiWei Wang

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Methods Mentioned

BETA
genotyping
GTPase

Software Mentioned

PASCAL
GeneNetwork
METAL
PLINK
GUIDANCE
IMPUTE2
SNPTEST
SHAPEIT2
Eigensoft
GenomeStudio

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