Mar 31, 2010

Multiple Common Variants for Celiac Disease Influencing Immune Gene Expression

Celiac.com 03/11/2010 - As part of an effort to investigate the possibility of multiple common variants for celiac disease influencing immune Gene Expression

The process by which a gene\'s coded information is converted into the structures present and operating in the cell. Expressed genes include those that are transcribed into mRNA and then translated into protein and those that are transcribed into RNA but not translated into protein (e.g., transfer and ribosomal RNAs).'); return false" style="color: rgb(80, 136, 1); text-decoration: underline; border-top-width: 0px; border-right-width: 0px; border-bottom-width: 0px; border-left-width: 0px; border-style: initial; border-color: initial; ">Gene Expression
, a team of more than sixty scientists recently worked together to conduct a second-generation genome-wide association study (GWAS) of 4,533 individuals with clinically proven celiac disease, along with 10,750 control subjects.

They genotyped a total of 113 selected SNPs with PGWAS <>

The GWAS included five European sample collections of celiac disease and control cases, including the celiac disease dataset reported previously. The team's stringent data quality control measures included calling genotypes using a custom algorithm on both large sample sets and, where possible, cases and controls together. The team tested 292,387 non-HLA

Human Leukocyte Antigen - elicit the strongest immunologic response in the body, and chromosome 6 is the genetic region that codes for these antigens. The genes that encode the class II molecules DQ2 and DQ8, the key genetic risk factors in celiac disease. Because the HLA complex is inherited intact as two haplotypes (one from each parent), siblings have 1 in 4 chance of being HLA-identical.'); return false" style="color: rgb(80, 136, 1); text-decoration: underline; border-top-width: 0px; border-right-width: 0px; border-bottom-width: 0px; border-left-width: 0px; border-style: initial; border-color: initial; ">HLA
SNPs from the Illumina Hap300 marker pool for association in 4,533 individuals with celiac disease and 10,750 control subjects of European descent. They also tested another 231,362 additional non-HLA markers from the Illumina Hap550 marker set for association in a subset of 3,796 individuals with celiac disease and 8,154 controls. All markers came from autosomes or the X chromosome. For both datasets, Genotype call rates were >99.9%.

The study showed over-dispersion factor of association test statistics comparable to that observed in other GWASs of this sample size. Factoring in missing genotypes for 737 cases with celiac disease genotyped on the Hap300 BeadChip and corresponding controls did not change the findings in any meaningful way. Variants from 13 new regions reached genome-wide significance (Pcombined < class="HelpLink" href="javascript:void(0)" onclick="">T-cell

A small lymph cell created in the thymus which orchestrates the immune system\'s response to infected or malignant cells. Also known as a T lymphocyte.'); return false" style="color: rgb(80, 136, 1); text-decoration: underline; border-top-width: 0px; border-right-width: 0px; border-bottom-width: 0px; border-left-width: 0px; border-style: initial; border-color: initial; ">T-cell selection.

The data suggested associations for 13 additional regions. Expression quantitative trait meta-analysis of 1,469 whole blood samples showed that 52.6% of tested loci (20 of 38 loci) had celiac risk variants corresponding with cis gene expression (P <>

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