Dataset Information

Autoimmune disease classification by inverse association with SNP alleles.

ABSTRACT: With multiple genome-wide association studies (GWAS) performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS), ankylosing spondylitis (AS), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), Crohn's disease (CD), and type 1 diabetes (T1D), as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways.

SUBMITTER: Sirota M

PROVIDER: S-EPMC2791168 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Autoimmune disease classification by inverse association with SNP alleles.

Sirota Marina M Schaub Marc A MA Batzoglou Serafim S Robinson William H WH Butte Atul J AJ

PLoS genetics 20091224 12

With multiple genome-wide association studies (GWAS) performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with mult ...[more]

PMID: 20041220

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Project description:BackgroundFrost is a limiting abiotic stress for the winter pea crop (Pisum sativum L.) and identifying the genetic determinants of frost tolerance is a major issue to breed varieties for cold northern areas. Quantitative trait loci (QTLs) have previously been detected from bi-parental mapping populations, giving an overview of the genome regions governing this trait. The recent development of high-throughput genotyping tools for pea brings the opportunity to undertake genetic association studies in order to capture a higher allelic diversity within large collections of genetic resources as well as to refine the localization of the causal polymorphisms thanks to the high marker density. In this study, a genome-wide association study (GWAS) was performed using a set of 365 pea accessions. Phenotyping was carried out by scoring frost damages in the field and in controlled conditions. The association mapping collection was also genotyped using an Illumina Infinium® BeadChip, which allowed to collect data for 11,366 single nucleotide polymorphism (SNP) markers.ResultsGWAS identified 62 SNPs significantly associated with frost tolerance and distributed over six of the seven pea linkage groups (LGs). These results confirmed 3 QTLs that were already mapped in multiple environments on LG III, V and VI with bi-parental populations. They also allowed to identify one locus, on LG II, which has not been detected yet and two loci, on LGs I and VII, which have formerly been detected in only one environment. Fifty candidate genes corresponding to annotated significant SNPs, or SNPs in strong linkage disequilibrium with the formers, were found to underlie the frost damage (FD)-related loci detected by GWAS. Additionally, the analyses allowed to define favorable haplotypes of markers for the FD-related loci and their corresponding accessions within the association mapping collection.ConclusionsThis study led to identify FD-related loci as well as corresponding favorable haplotypes of markers and representative pea accessions that might to be used in winter pea breeding programs. Among the candidate genes highlighted at the identified FD-related loci, the results also encourage further attention to the presence of C-repeat Binding Factors (CBF) as potential genetic determinants of the frost tolerance locus on LG VI.

Dataset Information

Autoimmune disease classification by inverse association with SNP alleles.

Publications

Autoimmune disease classification by inverse association with SNP alleles.

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