Logo image
Back
Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry
Journal article   Open access   Peer reviewed

Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry

F Yesim Demirci, Xingbin Wang, Jennifer A Kelly, David L Morris, M Michael Barmada, Eleanor Feingold, Amy H Kao, Kathy L Sivils, Sasha Bernatsky, Christian Pineau, …
Arthritis & rheumatology (Hoboken, N.J.), v 68(1), pp 174-183
Jan 2016
DOI: https://doi.org/10.1002/art.39403
PMID: 26316170
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4747422View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Adult Case-Control Studies Casein Kinase II - genetics Cell Cycle Proteins - genetics Chromosomes, Human, Pair 12 - genetics Chromosomes, Human, Pair 2 Chromosomes, Human, Pair 6 Chromosomes, Human, Pair 8 Computer Simulation Female Genetic Predisposition to Disease Genome-Wide Association Study Genotype HLA-DQ alpha-Chains - genetics HLA-DQ beta-Chains - genetics Humans Lupus Erythematosus, Systemic - genetics Major Histocompatibility Complex - genetics Male Middle Aged Polymorphism, Single Nucleotide Quantitative Trait Loci src-Family Kinases - genetics STAT4 Transcription Factor - genetics Tenascin - genetics Transcriptome White People - genetics
Genome-wide association studies (GWAS) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high-density genotyping platforms. Followup studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in subjects of European descent. This multistage study was undertaken to identify novel SLE loci. In stage 1, we conducted a new GWAS of SLE in a North American case-control sample of subjects of European ancestry (n = 1,166) genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. In stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta-analysis using an additional data set of subjects of European descent (>2,500 individuals), followed by replication of top meta-analysis findings in another data set of subjects of European descent (>10,000 individuals) in stage 3. As expected, our GWAS revealed the most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed the genome-wide significance threshold (P < 5 × 10(-8)). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also confirmed in the stage 1 discovery sample, and the strongest signals were observed at 2q32/STAT4 (P = 3.6 × 10(-7)) and at 8p23/BLK (P = 8.1 × 10(-6)). Stage 2 meta-analyses identified a new genome-wide significant SLE locus at 12q12 (meta P = 3.1 × 10(-8)), which was replicated in stage 3. Our multistage study identified and replicated a new SLE locus that warrants further followup in additional studies. Publicly available databases suggest that this newly identified SLE signal falls within a functionally relevant genomic region and near biologically important genes.

Metrics

5 Record Views
20 citations in Web of Science
22 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Rheumatology
Logo image