Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility

Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility Publisher Pubmed

Takeuchi M^{1, 2} ; Mizuki N² ; Meguro A² ; Ombrello MJ³ ; Kirino Y⁴ ; Satorius C¹ ; Le J¹ ; Blake M⁵ ; Erer B¹ ; Kawagoe T² ; Ustek D⁶ ; Tugaltutkun I⁷ ; Seyahi E⁸ ; Ozyazgan Y⁹ Show All Authors

Takeuchi M^{1, 2}
Mizuki N²
Meguro A²
Ombrello MJ³
Kirino Y⁴
Satorius C¹
Le J¹
Blake M⁵
Erer B¹
Kawagoe T²
Ustek D⁶
Tugaltutkun I⁷
Seyahi E⁸
Ozyazgan Y⁹
Sousa I^{10, 11}
Davatchi F¹²
Francisco V^{10, 11}
Shahram F¹²
Abdollahi BS¹²
Nadji A¹²
Shafiee NM¹²
Ghaderibarmi F¹²
Ohno S¹³
Ueda A⁴
Ishigatsubo Y⁴
Gadina M⁵
Oliveira SA^{10, 11}
Gul A¹⁴
Kastner DL¹
Remmers EF¹

Show Affiliations

1. Inflammatory Disease Section, National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD, United States
2. Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Japan
3. Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health, Bethesda, MD, United States
4. Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan
5. Translational Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health, Bethesda, MD, United States
6. Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey
7. Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
8. Department of Internal Medicine, Division of Rheumatology, Cerrahpas A Faculty of Medicine, Istanbul University, Istanbul, Turkey
9. Department of Ophthalmology, Cerrahpas A Faculty of Medicine, Istanbul University, Istanbul, Turkey
10. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
11. Instituto Gulbenkian de Ciencia, Oeiras, Portugal
12. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
13. Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
14. Department of Internal Medicine, Division of Rheumatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

Source: Nature Genetics Published:2017

Abstract

We analyzed 1,900 Turkish Behcet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B∗51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P < 5 × 10-8) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A-IL1B, was associated with both decreased IL-1α and increased IL-1β production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10-15). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behcet's disease susceptibility.

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Style	Citing Format
MLA	Takeuchi M, et al.. "Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility." Nature Genetics, vol. 49, no. 3, 2017, pp. 438-443.
APA	Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, Le J, Blake M, Erer B, Kawagoe T, Ustek D, Tugaltutkun I, Seyahi E, Ozyazgan Y, Sousa I, Davatchi F, Francisco V, Shahram F, Abdollahi BS, ... Remmers EF (2017). Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility. Nature Genetics, 49(3), 438-443.
Chicago	Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, Le J, et al.. "Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility." Nature Genetics 49, no. 3 (2017): 438-443.
Harvard	Takeuchi M et al. (2017) 'Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility', Nature Genetics, 49(3), pp. 438-443.
Vancouver	Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, et al.. Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility. Nature Genetics. 2017;49(3):438-443.
BibTex	@article{ author = {Takeuchi M and Mizuki N and Meguro A and Ombrello MJ and Kirino Y and Satorius C and Le J and Blake M and Erer B and Kawagoe T and Ustek D and Tugaltutkun I and Seyahi E and Ozyazgan Y and Sousa I and Davatchi F and Francisco V and Shahram F and Abdollahi BS and Nadji A and Shafiee NM and Ghaderibarmi F and Ohno S and Ueda A and Ishigatsubo Y and Gadina M and Oliveira SA and Gul A and Kastner DL and Remmers EF}, title = {Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility}, journal = {Nature Genetics}, volume = {49}, number = {3}, pages = {438-443}, year = {2017} }
RIS	TY - JOUR AU - Takeuchi M AU - Mizuki N AU - Meguro A AU - Ombrello MJ AU - Kirino Y AU - Satorius C AU - Le J AU - Blake M AU - Erer B AU - Kawagoe T AU - Ustek D AU - Tugaltutkun I AU - Seyahi E AU - Ozyazgan Y AU - Sousa I AU - Davatchi F AU - Francisco V AU - Shahram F AU - Abdollahi BS AU - Nadji A AU - Shafiee NM AU - Ghaderibarmi F AU - Ohno S AU - Ueda A AU - Ishigatsubo Y AU - Gadina M AU - Oliveira SA AU - Gul A AU - Kastner DL AU - Remmers EF TI - Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility JO - Nature Genetics VL - 49 IS - 3 SP - 438 EP - 443 PY - 2017 ER -

Style

Citing Format

MLA

Takeuchi M, et al.. "Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility." Nature Genetics, vol. 49, no. 3, 2017, pp. 438-443.

APA

Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, Le J, Blake M, Erer B, Kawagoe T, Ustek D, Tugaltutkun I, Seyahi E, Ozyazgan Y, Sousa I, Davatchi F, Francisco V, Shahram F, Abdollahi BS, ... Remmers EF (2017). Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility. Nature Genetics, 49(3), 438-443.

Chicago

Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, Le J, et al.. "Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility." Nature Genetics 49, no. 3 (2017): 438-443.

Harvard

Takeuchi M et al. (2017) 'Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility', Nature Genetics, 49(3), pp. 438-443.

Vancouver

Takeuchi M, Mizuki N, Meguro A, Ombrello MJ, Kirino Y, Satorius C, et al.. Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility. Nature Genetics. 2017;49(3):438-443.

BibTex

@article{ author = {Takeuchi M and Mizuki N and Meguro A and Ombrello MJ and Kirino Y and Satorius C and Le J and Blake M and Erer B and Kawagoe T and Ustek D and Tugaltutkun I and Seyahi E and Ozyazgan Y and Sousa I and Davatchi F and Francisco V and Shahram F and Abdollahi BS and Nadji A and Shafiee NM and Ghaderibarmi F and Ohno S and Ueda A and Ishigatsubo Y and Gadina M and Oliveira SA and Gul A and Kastner DL and Remmers EF}, title = {Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility}, journal = {Nature Genetics}, volume = {49}, number = {3}, pages = {438-443}, year = {2017} }

RIS

TY - JOUR
AU - Takeuchi M
AU - Mizuki N
AU - Meguro A
AU - Ombrello MJ
AU - Kirino Y
AU - Satorius C
AU - Le J
AU - Blake M
AU - Erer B
AU - Kawagoe T
AU - Ustek D
AU - Tugaltutkun I
AU - Seyahi E
AU - Ozyazgan Y
AU - Sousa I
AU - Davatchi F
AU - Francisco V
AU - Shahram F
AU - Abdollahi BS
AU - Nadji A
AU - Shafiee NM
AU - Ghaderibarmi F
AU - Ohno S
AU - Ueda A
AU - Ishigatsubo Y
AU - Gadina M
AU - Oliveira SA
AU - Gul A
AU - Kastner DL
AU - Remmers EF
TI - Dense Genotyping of Immune-Related Loci Implicates Host Responses to Microbial Exposure in Behcet's Disease Susceptibility
JO - Nature Genetics
VL - 49
IS - 3
SP - 438
EP - 443
PY - 2017
ER -

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Abstract