ReviewGenome-wide association studies in type 1 diabetes, inflammatory bowel disease and other immune-mediated disorders
Section snippets
Approaches to analysis of complex genetic traits
Prior to the availability of platforms for genome-wide association (GWA) analyses, efforts to uncover the genetic underpinnings of a given complex disease were focused on association studies of ‘candidate’ genes, selected based on biological reasoning that the gene product was involved in the pathogenesis of the disease, as well as family-based linkage studies. Some extremely important discoveries of type 1 diabetes variants were made by these approaches, including identification of strong
Type 1 diabetes
Type 1 diabetes (T1D) is a disease that results from autoimmune destruction of pancreatic beta cells, resulting in a lack of production of insulin. T1D represents approximately 10% of all cases of diabetes and is most prevalent in populations of European ancestry, where the is ample evidence of increased annual incidence during the past 5 decades [42], [43].
T1D risk is strongly influenced by multiple genetic loci and as yet poorly understood environmental factors. The disease is highly
Inflammatory bowel disease
Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology involving multiple genes and environmental factors. The two IBD subtypes, Crohn's disease (CD) and ulcerative colitis (UC) present most commonly during the second and third decades of life [72]. They are characterized respectively by confluent inflammation of the colonic mucosa (UC) and discontinuous transmural intestinal inflammation (CD). IBD is thought to develop as a result of dysregulation of immune
Other immune-mediated disorders
There are hundreds of immune-mediated diseases known to impact humans. However, some are much more prevalent than others, with asthma, ankylosing spondylitis, systemic lupus erythematosus and rheumatoid arthritis being among the most common. As such, for these given disorders there have been sufficient sample sizes to also investigate them with the GWA approach.
Moffatt et al. [112] reported a GWA of 500,000 SNPs in childhood onset asthma where they genotyped nearly 1000 patients and 1200
Discussion
The advent of genome-wide platforms to capture SNP variation has enhanced our understanding of the genetic basis of complex diseases, such as type 1 diabetes and inflammatory bowel disease. Indeed, over the last 3 years, notable discoveries of variants impacting multiple complex diseases and related traits have been reported, and replicated by independent groups. Type 1 diabetes and inflammatory bowel disease have been success stories in this context, yielding many new genes and, indeed, have
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Inflammatory bowel disease
2011, Primary Care - Clinics in Office PracticeCitation Excerpt :Hence, despite the fact that genetic factors are important, more so in CD than UC, it is evident that environmental factors also play a key role. Genome-wide association studies have revealed more than 40 susceptibility loci for IBD, some associated specifically with either CD or UC and others associated with both.15 Prominent among these findings are the IBD1 gene encoding the protein NOD2 (also called CARD15) in CD, OCTN1/2 within the IBD5 locus in CD and UC, ATG16L in CD, IRGM1 in CD, and IL23R in CD and UC.16
Enhancement of deoxyribonucleic acid microarray performance using post-hybridization signal amplification
2010, Analytica Chimica ActaCitation Excerpt :DNA microarray technology has revolutionized nucleic acid-based research due to its ability to run a vast number of parallel reactions simultaneously and provide high-throughput data analysis. While traditional uses of microarrays have focused predominantly on gene expression profiling and genotype analysis, the broad utility of the technology has prompted its application to a number of disparate fields including autoimmune disease analysis [1,2], environmental studies [3,4], cancer genomics [5–7], and biodefense [8]. Microarray performance is critically dependent upon its ability to demonstrate sufficient specificity and sensitivity for targets.
Identification of key regulatory genes and their working mechanisms in type 1 diabetes
2023, BMC Medical GenomicsOutcomes of pancreas transplantation in patients with underlying inflammatory bowel disease: a retrospective case series
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2023, Critical Reviews in Food Science and NutritionThe role of autoimmunity-related gene CLEC16A in the B cell receptor-mediated HLA class II pathway
2020, Journal of Immunology
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