Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome‐Wide Association Study
Copyright policy )Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome‐Wide Association Study
ObjectiveTakayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis.MethodsTwo independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1‐Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis.ResultsWe identified genetic susceptibility loci for Takayasu arteritis with a genome‐wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10−9), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10−8), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10−10). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin‐like receptor gene LILRB3 (P = 2.29 × 10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10−5) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B.ConclusionOur findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.
- Mayo Clinic United States
- Boston University United States
- Johns Hopkins University United States
- University of Michigan–Ann Arbor United States
- Cleveland Clinic United States
genetic association, Turkey, Chromosomes, Human, Pair 21, genotype, chromosome 19q, genetic risk, gene cluster, DISEASE, Turkey (republic), Cohort Studies, quantitative trait locus, single nucleotide polymorphism, genetic variability, Odds Ratio, odds ratio, Disease, genetics, lilra3 gene, Receptors, Immunologic, POPULATION, Visualization, Ribosomal Protein S9, ptk2b gene, immunoglobulin receptor, aorta arch syndrome, ANKYLOSING-SPONDYLITIS, lilrb3 gene, Classification, cohort analysis, LILRB3 protein, chromosome 21, genotyping technique, priority journal, ribosomal protein s9 gene, spacer DNA, North American, Ribosomal Proteins, Population, European Continental Ancestry Group, 610, interleukin 6, IL6 protein, IL6 protein, human, Caucasian, European, ribosomal protein S9, CLASSIFICATION, Article, White People, Ankylosing-Spondylitis, ribosome protein, chromosome 21q, Rheumatology, Antigens, CD, 616, Health Sciences, Humans, controlled study, Genetic Predisposition to Disease, human, quality control, gene, gene identification, leukocyte antigen, Interleukin-6, [No Keywords], LILRB3 protein, human, case control study, major clinical study, Takayasu Arteritis, pcsk5 gene, ppm1g gene, TURKEY, Case-Control Studies, North America, Turk (people), VISUALIZATION, genetic predisposition, nrbp1 gene, genetic susceptibility, Genome-Wide Association Study
genetic association, Turkey, Chromosomes, Human, Pair 21, genotype, chromosome 19q, genetic risk, gene cluster, DISEASE, Turkey (republic), Cohort Studies, quantitative trait locus, single nucleotide polymorphism, genetic variability, Odds Ratio, odds ratio, Disease, genetics, lilra3 gene, Receptors, Immunologic, POPULATION, Visualization, Ribosomal Protein S9, ptk2b gene, immunoglobulin receptor, aorta arch syndrome, ANKYLOSING-SPONDYLITIS, lilrb3 gene, Classification, cohort analysis, LILRB3 protein, chromosome 21, genotyping technique, priority journal, ribosomal protein s9 gene, spacer DNA, North American, Ribosomal Proteins, Population, European Continental Ancestry Group, 610, interleukin 6, IL6 protein, IL6 protein, human, Caucasian, European, ribosomal protein S9, CLASSIFICATION, Article, White People, Ankylosing-Spondylitis, ribosome protein, chromosome 21q, Rheumatology, Antigens, CD, 616, Health Sciences, Humans, controlled study, Genetic Predisposition to Disease, human, quality control, gene, gene identification, leukocyte antigen, Interleukin-6, [No Keywords], LILRB3 protein, human, case control study, major clinical study, Takayasu Arteritis, pcsk5 gene, ppm1g gene, TURKEY, Case-Control Studies, North America, Turk (people), VISUALIZATION, genetic predisposition, nrbp1 gene, genetic susceptibility, Genome-Wide Association Study
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).97 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!