Common variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency
Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 × 10-8) loci and association with a rare IFIH1 va...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishing Group
2016
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| _version_ | 1797093583105294336 |
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| author | Bronson, P Chang, D Bhangale, T Seldin, M Ortmann, W Ferreira, R Urcelay, E Pereira, L Martin, J Plebani, A Lougaris, V Friman, V Freiberger, T Litzman, J Thon, V Pan-Hammarström, Q Hammarström, L Graham, R Behrens, T |
| author_facet | Bronson, P Chang, D Bhangale, T Seldin, M Ortmann, W Ferreira, R Urcelay, E Pereira, L Martin, J Plebani, A Lougaris, V Friman, V Freiberger, T Litzman, J Thon, V Pan-Hammarström, Q Hammarström, L Graham, R Behrens, T |
| author_sort | Bronson, P |
| collection | OXFORD |
| description | Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 × 10-8) loci and association with a rare IFIH1 variant (p.Ile923Val). Peak new variants (PVT1, P = 4.3 × 10-11; ATG13-AMBRA1, P = 6.7 × 10-10; AHI1, P = 8.4 × 10-10; CLEC16A, P = 1.4 × 10-9) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3+ regulatory T cells. Pathway analysis of the meta-analysis results showed striking association with the KEGG pathway for IgA production (pathway P < 0.0001), with 22 of the 30 annotated pathway genes containing at least one variant with P ≤ 0.05 in the IgAD meta-analysis. These data suggest that a complex network of genetic effects, including genes known to influence the biology of IgA production, contributes to IgAD. |
| first_indexed | 2024-03-07T04:02:36Z |
| format | Journal article |
| id | oxford-uuid:c51900a1-2af4-46ab-ad05-3f29b431083e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:02:36Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:c51900a1-2af4-46ab-ad05-3f29b431083e2022-03-27T06:28:25ZCommon variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiencyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c51900a1-2af4-46ab-ad05-3f29b431083eEnglishSymplectic Elements at OxfordNature Publishing Group2016Bronson, PChang, DBhangale, TSeldin, MOrtmann, WFerreira, RUrcelay, EPereira, LMartin, JPlebani, ALougaris, VFriman, VFreiberger, TLitzman, JThon, VPan-Hammarström, QHammarström, LGraham, RBehrens, TSelective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 × 10-8) loci and association with a rare IFIH1 variant (p.Ile923Val). Peak new variants (PVT1, P = 4.3 × 10-11; ATG13-AMBRA1, P = 6.7 × 10-10; AHI1, P = 8.4 × 10-10; CLEC16A, P = 1.4 × 10-9) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3+ regulatory T cells. Pathway analysis of the meta-analysis results showed striking association with the KEGG pathway for IgA production (pathway P < 0.0001), with 22 of the 30 annotated pathway genes containing at least one variant with P ≤ 0.05 in the IgAD meta-analysis. These data suggest that a complex network of genetic effects, including genes known to influence the biology of IgA production, contributes to IgAD. |
| spellingShingle | Bronson, P Chang, D Bhangale, T Seldin, M Ortmann, W Ferreira, R Urcelay, E Pereira, L Martin, J Plebani, A Lougaris, V Friman, V Freiberger, T Litzman, J Thon, V Pan-Hammarström, Q Hammarström, L Graham, R Behrens, T Common variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency |
| title | Common variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency |
| title_full | Common variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency |
| title_fullStr | Common variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency |
| title_full_unstemmed | Common variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency |
| title_short | Common variants at PVT1, ATG13–AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency |
| title_sort | common variants at pvt1 atg13 ambra1 ahi1 and clec16a are associated with selective iga deficiency |
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