ID

45000

Description

Principal Investigator: Elaine F. Remmers, PhD, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA MeSH: Behcet Syndrome https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000272 *Introduction* Behçet's disease (BD) is a genetically complex multisystem disease of unknown etiology, characterized by recurrent inflammatory attacks affecting orogenital mucosa, eyes, skin, joints, blood vessels, and less frequently, the central nervous system and gastrointestinal tract. Family studies suggest a genetically complex contribution to BD. With the exception of HLA-B51, which explains less than 20% of the genetic risk, the identities of alleles that are responsible for the complex inheritance of this disease have remained unclear. *Aim* To identify genes that contribute to BD susceptibility. *Methods* A genome-wide association study was undertaken with 311,459 informative and high quality SNPs in a collection of 1215 BD patients and 1278 healthy controls from Turkey using a beadchip microarray assay (Infinium SNP genotype assay, Illumina). HLA-B types were determined with a reverse sequence-specific oligonucleotide method (One Lambda). Regions with evidence for association were fine-mapped using Sequenom iPLEX gold assays. Disease-associated SNPs were genotyped in additional ethnically matched case/control collections from diverse genetic backgrounds, including a total of 2430 cases and 2660 controls, using TaqMan SNP genotype assays. Association data were combined in a meta-analysis of all the collections. *Results* We confirmed the known association with HLA-B51 and found evidence for a second, independent susceptibility locus in the Class I region of the MHC. In addition, we identified one SNP with genome-wide evidence for disease association (P 5.0 x 10sup-8/sup) within the gene encoding the immunoregulatory cytokine, interleukin-10 (IL10). A meta-analysis of the data from all the collections established associations with the IL10 variant (rs1518111, P = 3.54 x 10sup-18/sup, odds ratio 1.45 with 95% confidence interval 1.34 to 1.58) and with a variant located between the interleukin-23 receptor (IL23R) and interleukin 12 receptor β2 (IL12RB2) genes (rs924080, P = 6.69 x 10sup-9/sup, odds ratio 1.28 with 95% confidence interval 1.18 to 1.39). The disease-associated IL10 variant was associated with diminished mRNA expression and low protein production by cells obtained from healthy blood donors. *Conclusions* These data suggest that genetically encoded low production of IL-10 increases risk of BD and suggest novel interventional targets in the IL-10 and IL-23 pathways. Note: The submitted data are the genotypes of the 311,459 SNPs in 1215 cases and 1278 controls.

Link

https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000272

Keywords

  1. 7/4/22 7/4/22 - Dr. Christian Niklas
  2. 10/12/22 10/12/22 - Adrian Schulz
Copyright Holder

Elaine F. Remmers, PhD, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

Uploaded on

July 4, 2022

DOI

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License

Creative Commons BY 4.0

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dbGaP phs000272 Genome-Wide Association Study of Behçet's Disease (Turkish)

This data table contains a listing of subjects, subject consents and affection status for Behcet's Disease.

pht001444
Description

pht001444

Subject ID
Description

SUBJID

Data type

string

Alias
UMLS CUI [1,1]
C2348585
Consent group as determined by DAC
Description

CONSENT

Data type

text

Alias
UMLS CUI [1,1]
C0021430
Case control status of the subject
Description

AFFECTION_STATUS

Data type

text

Alias
UMLS CUI [1,1]
C2348568

Similar models

This data table contains a listing of subjects, subject consents and affection status for Behcet's Disease.

Name
Type
Description | Question | Decode (Coded Value)
Data type
Alias
Item Group
pht001444
SUBJID
Item
Subject ID
string
C2348585 (UMLS CUI [1,1])
Item
Consent group as determined by DAC
text
C0021430 (UMLS CUI [1,1])
Code List
Consent group as determined by DAC
CL Item
General Research Use (GRU) (1)
Item
Case control status of the subject
text
C2348568 (UMLS CUI [1,1])
Code List
Case control status of the subject
CL Item
Control (1)
C0009932 (UMLS CUI [1,1])
CL Item
Case (2)
C1698493 (UMLS CUI [1,1])

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