Showing papers by "Alexandra Zhernakova published in 2012"
Manchester Academic Health Science Centre1, National Institute for Health Research2, Broad Institute3, Brigham and Women's Hospital4, North Shore-LIJ Health System5, University Medical Center Groningen6, Leiden University7, University of Texas MD Anderson Cancer Center8, Karolinska University Hospital9, Karolinska Institutet10, Genome Institute of Singapore11, Wellcome Trust Sanger Institute12, University of Virginia13, Hospital Clínico San Carlos14, Umeå University15, Spanish National Research Council16
TL;DR: This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations and refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci.
Abstract: Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.
612 citations
Queen Mary University of London1, University of Cambridge2, University of Kiel3, University of Plymouth4, University of London5, Wellcome Trust Sanger Institute6, University of Oxford7, University of Virginia8, University of Groningen9, Leiden University10, Newcastle University11, Guy's and St Thomas' NHS Foundation Trust12, University of Freiburg13, NHS Blood and Transplant14, University College London15, University of Edinburgh16, Cincinnati Children's Hospital Medical Center17, Leiden University Medical Center18, Technische Universität München19, University of Sassari20
TL;DR: Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry.
Abstract: Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry
43 citations
TL;DR: A basic principle in genetic association studies is to evaluate multiple cohorts to validate observed findings, and both single-nucleotide polymorphisms in several RA cohorts with radiological follow-up data were studied.
Abstract: The severity of joint destruction in rheumatoid arthritis (RA) is highly variable between patients. Recent twin and population studies indicated that the severity of joint destruction is influenced by genetic factors.1 ,2 Previously, we reported the association of rs10818488 ( TRAF1-C5 ) and rs675520 ( TNFAIP3-OLIG3 ) with progression of joint destruction.3 ,4 The genes near these loci encode for tumour necrosis factor receptor-associated factor-1 ( TRAF1 ), complement component-5 ( C5 ) and tumour necrosis factor α-induced protein-3 ( TNFAIP3 ; a protein that inhibits NF-κ B activation). A basic principle in genetic association studies is to evaluate multiple cohorts to validate observed findings. We therefore studied both single-nucleotide polymorphisms in several RA cohorts with radiological follow-up data.
Six thousand two hundred and eighty-two x-rays of 2666 RA patients were studied: 147 patients from Lund (Sweden), 385 patients from Sheffield (UK), 285 patients from Iceland, 384 patients from the North American Rheumatoid Arthritis Consortium (NARAC), 756 patients from the National Databank of Rheumatic Diseases (NDB), 113 patients from Wichita and 596 patients from the Leiden Early Arthritis Clinic (Leiden-EAC) cohort (table 1). Detailed information on these datasets is provided elsewhere.2 ,5,–,10 …
20 citations
Journal Article•
1 citations