{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T08:49:48Z","timestamp":1782118188416,"version":"3.54.5"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum. Genet."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Selective immunoglobulin A deficiency (IgAD) is the most prevalent primary immunodeficiency and frequently coexists with autoimmune diseases (ADs), suggesting a shared genetic etiology. While genome-wide association studies (GWAS) have identified only a few risk loci for IgAD and hundreds for ADs, systematic cross-trait analyses are lacking, leaving the shared genetic architecture and underlying mechanisms poorly understood. In this study, we analyzed summary statistics from large-scale GWAS of IgAD and 10 common ADs. Cross-trait GWAS meta-analysis identified 51 pleiotropic loci significantly associated with IgAD and at least one AD (p &lt; 5\u00d710\u207b\u2078), 31 of which were novel for IgAD. Colocalization analysis further supported 33 shared loci between IgAD and ADs, including 19 novel IgAD loci, such as those near\n                    <jats:italic>TNFAIP3<\/jats:italic>\n                    ,\n                    <jats:italic>CD28<\/jats:italic>\n                    ,\n                    <jats:italic>IRF4<\/jats:italic>\n                    ,\n                    <jats:italic>STAT4<\/jats:italic>\n                    ,\n                    <jats:italic>SH2B3<\/jats:italic>\n                    ,\n                    <jats:italic>APOBR<\/jats:italic>\n                    and\n                    <jats:italic>RAD51B<\/jats:italic>\n                    . Gene-level analysis revealed shared pathways involved in T-cell differentiation and the intestinal immune network for IgA production. Tissue heritability analysis identified whole blood and the intestine as critical tissues, while single-cell RNA sequencing (scRNA-seq) highlighted B cell subtypes in the peripheral blood and gut as the most affected cell types in IgAD and ADs. Mendelian randomization further demonstrated bidirectional causal relationships between IgAD and several ADs. Our findings reveal a shared genetic architecture between IgAD and ADs, highlighting common functional mechanisms and providing insights into their biological interplay and potential immune-based therapies.\n                  <\/jats:p>","DOI":"10.1007\/s00439-026-02850-5","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T08:14:50Z","timestamp":1782116090000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the shared genetic architecture between selective immunoglobulin A deficiency and autoimmune diseases"],"prefix":"10.1007","volume":"145","author":[{"given":"Xiao","family":"Dang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Qingyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caicai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huidong","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Lung","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0063-6327","authenticated-orcid":false,"given":"Wanling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"2850_CR1","doi-asserted-by":"publisher","first-page":"D886","DOI":"10.1093\/nar\/gkae1142","volume":"53","author":"S Abdulla","year":"2025","unstructured":"Abdulla S, Aevermann B, Assis P, Badajoz S, Bell SM, Bezzi E, Cakir B, Chaffer J, Chambers S, Cherry JM et al (2025) CZ CELLxGENE Discover: a single-cell data platform for scalable exploration, analysis and modeling of aggregated data. Nucl Acids Res 53:D886-d900. https:\/\/doi.org\/10.1093\/nar\/gkae1142","journal-title":"Nucl Acids Res"},{"key":"2850_CR2","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1159\/000323903","volume":"156","author":"A Aghamohammadi","year":"2011","unstructured":"Aghamohammadi A, Abolhassani H, Biglari M, Abolmaali S, Moazzami K, Tabatabaeiyan M, Asgarian-Omran H, Parvaneh N, Mirahmadian M, Rezaei N (2011) Analysis of switched memory B cells in patients with IgA deficiency. Int Arch Allergy Immunol 156:462\u2013468. https:\/\/doi.org\/10.1159\/000323903","journal-title":"Int Arch Allergy Immunol"},{"key":"2850_CR3","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar S, Gonz\u00e1lez-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, Rambow F, Marine J-C, Geurts P, Aerts J et al (2017) SCENIC: single-cell regulatory network inference and clustering. Nat Methods 14:1083\u20131086. https:\/\/doi.org\/10.1038\/nmeth.4463","journal-title":"Nat Methods"},{"key":"2850_CR4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jaut.2019.01.011","volume":"99","author":"L Amaya-Uribe","year":"2019","unstructured":"Amaya-Uribe L, Rojas M, Azizi G, Anaya JM, Gershwin ME (2019) Primary immunodeficiency and autoimmunity: A comprehensive review. J Autoimmun 99:52\u201372. https:\/\/doi.org\/10.1016\/j.jaut.2019.01.011","journal-title":"J Autoimmun"},{"key":"2850_CR5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton A, Abecasis GR, Altshuler DM, Durbin RM, Abecasis GR, Bentley DR, Chakravarti A, Clark AG, Donnelly P, Eichler EE et al (2015) A global reference for human genetic variation. Nature 526:68\u201374. https:\/\/doi.org\/10.1038\/nature15393","journal-title":"Nature"},{"key":"2850_CR6","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1038\/ng.3675","volume":"48","author":"PG Bronson","year":"2016","unstructured":"Bronson PG, Chang D, Bhangale T, Seldin MF, Ortmann W, Ferreira RC, Urcelay E, Pereira LF, Martin J, Plebani A (2016) Common variants at PVT1, ATG13\u2013AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nature genetics 48:1425\u20131429","journal-title":"Nature genetics"},{"key":"2850_CR7","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ng.3211","volume":"47","author":"BK Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Patterson N, Daly MJ, Price AL, Neale BM, Schizophrenia Working Group of the Psychiatric Genomics, C (2015) LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet 47:291\u2013295. https:\/\/doi.org\/10.1038\/ng.3211","journal-title":"Nat Genet"},{"key":"2850_CR8","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1038\/ng.3406","volume":"47","author":"B Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Loh PR, Duncan L, Perry JR, Patterson N, Robinson EB et al (2015) An atlas of genetic correlations across human diseases and traits. Nat Genet 47:1236\u20131241. https:\/\/doi.org\/10.1038\/ng.3406","journal-title":"Nat Genet"},{"key":"2850_CR9","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/s41586-021-03552-w","volume":"594","author":"J Chiou","year":"2021","unstructured":"Chiou J, Geusz RJ, Okino M-L, Han JY, Miller M, Melton R, Beebe E, Benaglio P, Huang S, Korgaonkar K (2021) Interpreting type 1 diabetes risk with genetics and single-cell epigenomics. Nature 594:398\u2013402","journal-title":"Nature"},{"key":"2850_CR10","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","volume":"369","author":"G Consortium","year":"2020","unstructured":"Consortium G (2020) The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369:1318\u20131330","journal-title":"Science"},{"key":"2850_CR11","doi-asserted-by":"crossref","unstructured":"International IBD Genetics Consortium (IIBDGC), Agliardi C, Alfredsson L, Alizadeh M, Anderson C, Andrews R, S\u00f8ndergaard HB, Baker A, Band G (2013) Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Gent 45:1353\u20131360","DOI":"10.1038\/ng.2770"},{"key":"2850_CR12","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.jhep.2021.04.055","volume":"75","author":"HJ Cordell","year":"2021","unstructured":"Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor S-S, Gervais O (2021) An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs. J Hepatol 75:572\u2013581","journal-title":"J Hepatol"},{"key":"2850_CR13","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/ng.3760","volume":"49","author":"KM De Lange","year":"2017","unstructured":"De Lange KM, Moutsianas L, Lee JC, Lamb CA, Luo Y, Kennedy NA, Jostins L, Rice DL, Gutierrez-Achury J, Ji S-G (2017) Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 49:256\u2013261","journal-title":"Nat Genet"},{"key":"2850_CR14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004219","volume":"11","author":"CA de Leeuw","year":"2015","unstructured":"de Leeuw CA, Mooij JM, Heskes T, Posthuma D (2015) MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol 11:e1004219. https:\/\/doi.org\/10.1371\/journal.pcbi.1004219","journal-title":"PLoS Comput Biol"},{"key":"2850_CR15","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1002\/art.41532","volume":"73","author":"X Dong","year":"2021","unstructured":"Dong X, Antao OQ, Song W, Sanchez GM, Zembrzuski K, Koumpouras F, Lemenze A, Craft J, Weinstein JS (2021) Type I Interferon-activated STAT4 regulation of follicular helper T cell-dependent cytokine and immunoglobulin production in lupus. Arthritis Rheumatol 73:478\u2013489. https:\/\/doi.org\/10.1002\/art.41532","journal-title":"Arthritis Rheumatol"},{"key":"2850_CR16","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/s41586-023-06563-x","volume":"622","author":"GH Eldjarn","year":"2023","unstructured":"Eldjarn GH, Ferkingstad E, Lund SH, Helgason H, Magnusson OT, Gunnarsdottir K, Olafsdottir TA, Halldorsson BV, Olason PI, Zink F et al (2023) Large-scale plasma proteomics comparisons through genetics and disease associations. Nature 622:348\u2013358. https:\/\/doi.org\/10.1038\/s41586-023-06563-x","journal-title":"Nature"},{"key":"2850_CR17","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41586-021-03852-1","volume":"597","author":"R Elmentaite","year":"2021","unstructured":"Elmentaite R, Kumasaka N, Roberts K, Fleming A, Dann E, King HW, Kleshchevnikov V, Dabrowska M, Pritchard S, Bolt L et al (2021) Cells of the human intestinal tract mapped across space and time. Nature 597:250\u2013255. https:\/\/doi.org\/10.1038\/s41586-021-03852-1","journal-title":"Nature"},{"key":"2850_CR18","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41588-018-0081-4","volume":"50","author":"HK Finucane","year":"2018","unstructured":"Finucane HK, Reshef YA, Anttila V, Slowikowski K, Gusev A, Byrnes A, Gazal S, Loh PR, Lareau C, Shoresh N et al (2018) Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat Genet 50:621\u2013629. https:\/\/doi.org\/10.1038\/s41588-018-0081-4","journal-title":"Nat Genet"},{"key":"2850_CR19","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/s41467-020-20885-8","volume":"12","author":"CN Foley","year":"2021","unstructured":"Foley CN, Staley JR, Breen PG, Sun BB, Kirk PDW, Burgess S, Howson JMM (2021) A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits. Nat Commun 12:764. https:\/\/doi.org\/10.1038\/s41467-020-20885-8","journal-title":"Nat Commun"},{"key":"2850_CR20","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/s41588-022-01087-y","volume":"54","author":"S Gazal","year":"2022","unstructured":"Gazal S, Weissbrod O, Hormozdiari F, Dey KK, Nasser J, Jagadeesh KA, Weiner DJ, Shi H, Fulco CP, O\u2019Connor LJ (2022) Combining SNP-to-gene linking strategies to identify disease genes and assess disease omnigenicity. Nat Genet 54:827\u2013836","journal-title":"Nat Genet"},{"key":"2850_CR21","doi-asserted-by":"publisher","first-page":"D1311","DOI":"10.1093\/nar\/gkaa840","volume":"49","author":"M Ghoussaini","year":"2021","unstructured":"Ghoussaini M, Mountjoy E, Carmona M, Peat G, Schmidt EM, Hercules A, Fumis L, Miranda A, Carvalho-Silva D, Buniello A (2021) Open targets genetics: systematic identification of trait-associated genes using large-scale genetics and functional genomics. Nucleic Acids Res 49:D1311\u2013D1320","journal-title":"Nucleic Acids Res"},{"key":"2850_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383","volume":"10","author":"C Giambartolomei","year":"2014","unstructured":"Giambartolomei C, Vukcevic D, Schadt EE, Franke L, Hingorani AD, Wallace C, Plagnol V (2014) Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet 10:e1004383. https:\/\/doi.org\/10.1371\/journal.pgen.1004383","journal-title":"PLoS Genet"},{"key":"2850_CR23","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1130","volume":"9","author":"C Grosserichter-Wagener","year":"2020","unstructured":"Grosserichter-Wagener C, Franco-Gallego A, Ahmadi F, Moncada-V\u00e9lez M, Dalm VA, Rojas JL, Orrego JC, Correa Vargas N, Hammarstr\u00f6m L, Schreurs MW et al (2020) Defective formation of IgA memory B cells, Th1 and Th17 cells in symptomatic patients with selective IgA deficiency. Clin Transl Immun 9:e1130. https:\/\/doi.org\/10.1002\/cti2.1130","journal-title":"Clin Transl Immun"},{"key":"2850_CR24","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/ng.3506","volume":"48","author":"A Gusev","year":"2016","unstructured":"Gusev A, Ko A, Shi H, Bhatia G, Chung W, Penninx BW, Jansen R, de Geus EJ, Boomsma DI, Wright FA et al (2016) Integrative approaches for large-scale transcriptome-wide association studies. Nat Genet 48:245\u2013252. https:\/\/doi.org\/10.1038\/ng.3506","journal-title":"Nat Genet"},{"key":"2850_CR25","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","author":"G Hemani","year":"2018","unstructured":"Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, Laurin C, Burgess S, Bowden J, Langdon R et al (2018) The MR-Base platform supports systematic causal inference across the human phenome. Elife. https:\/\/doi.org\/10.7554\/eLife.34408","journal-title":"Elife"},{"key":"2850_CR26","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1038\/s41588-022-01213-w","volume":"54","author":"K Ishigaki","year":"2022","unstructured":"Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, Amariuta T, Too CL, Laufer VA, Scott IC (2022) Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis. Nature Genet 54:1640\u20131651","journal-title":"Nature Genet"},{"key":"2850_CR27","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/ng.3680","volume":"48","author":"Y Jin","year":"2016","unstructured":"Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Brownson KM, Holland PJ, Birlea SA, Siebert J, Hartmann A et al (2016) Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet 48:1418\u20131424. https:\/\/doi.org\/10.1038\/ng.3680","journal-title":"Nat Genet"},{"key":"2850_CR28","doi-asserted-by":"publisher","first-page":"205873841877945","DOI":"10.1177\/2058738418779458","volume":"32","author":"NE Karaca","year":"2018","unstructured":"Karaca NE, Severcan EU, Bilgin BG, Azarsiz E, Akarcan S, Gunayd\u0131n NC, Gulez N, Genel F, Aksu G, Kutukculer N (2018) Familial inheritance and screening of first-degree relatives in common variable immunodeficiency and immunoglobulin A deficiency patients. Int J Immunopathol Pharmacol 32:2058738418779458. https:\/\/doi.org\/10.1177\/2058738418779458","journal-title":"Int J Immunopathol Pharmacol"},{"key":"2850_CR29","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1093\/ibd\/izad089","volume":"29","author":"M Khrom","year":"2023","unstructured":"Khrom M, Li D, Naito T, Lee HS, Botwin GJ, Potdar AA, Boucher G, Yang S, Mengesha E, Dube S et al (2023) Sex-dimorphic analyses identify novel and sex-specific genetic associations in inflammatory bowel disease. Inflamm Bowel Dis 29:1622\u20131632. https:\/\/doi.org\/10.1093\/ibd\/izad089","journal-title":"Inflamm Bowel Dis"},{"key":"2850_CR30","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/s41588-022-01025-y","volume":"54","author":"K Kundu","year":"2022","unstructured":"Kundu K, Tardaguila M, Mann AL, Watt S, Ponstingl H, Vasquez L, Von Schiller D, Morrell NW, Stegle O, Pastinen T (2022) Genetic associations at regulatory phenotypes improve fine-mapping of causal variants for 12 immune-mediated diseases. Nature genetics 54:251\u2013262","journal-title":"Nature genetics"},{"key":"2850_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00909","volume":"9","author":"AL Lemarquis","year":"2018","unstructured":"Lemarquis AL, Einarsdottir HK, Kristjansdottir RN, Jonsdottir I, Ludviksson BR (2018) Transitional B Cells and TLR9 Responses Are Defective in Selective IgA Deficiency. Front Immunol 9:909. https:\/\/doi.org\/10.3389\/fimmu.2018.00909","journal-title":"Front Immunol"},{"key":"2850_CR32","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s10238-022-00968-0","volume":"23","author":"R Maffei","year":"2023","unstructured":"Maffei R, Fiorcari S, Atene CG, Martinelli S, Mesini N, Pilato F, Lagreca I, Barozzi P, Riva G, Nasillo V et al (2023) The dynamic functions of IRF4 in B cell malignancies. Clin Exp Med 23:1171\u20131180. https:\/\/doi.org\/10.1007\/s10238-022-00968-0","journal-title":"Clin Exp Med"},{"key":"2850_CR33","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1053\/j.gastro.2021.02.053","volume":"160","author":"JM Moll","year":"2021","unstructured":"Moll JM, Myers PN, Zhang C, Eriksen C, Wolf J, Appelberg KS, Lindberg G, Bahl MI, Zhao H, Pan-Hammarstr\u00f6m Q et al (2021) Gut microbiota perturbation in IgA deficiency is influenced by IgA-autoantibody status. Gastroenterology 160:2423-2434.e2425. https:\/\/doi.org\/10.1053\/j.gastro.2021.02.053","journal-title":"Gastroenterology"},{"key":"2850_CR34","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/s41588-021-00945-5","volume":"53","author":"E Mountjoy","year":"2021","unstructured":"Mountjoy E, Schmidt EM, Carmona M, Schwartzentruber J, Peat G, Miranda A, Fumis L, Hayhurst J, Buniello A, Karim MA (2021) An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci. Nat Genet 53:1527\u20131533","journal-title":"Nat Genet"},{"key":"2850_CR35","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/s41586-021-03446-x","volume":"593","author":"J Nasser","year":"2021","unstructured":"Nasser J, Bergman DT, Fulco CP, Guckelberger P, Doughty BR, Patwardhan TA, Jones TR, Nguyen TH, Ulirsch JC, Lekschas F (2021) Genome-wide enhancer maps link risk variants to disease genes. Nature 593:238\u2013243","journal-title":"Nature"},{"key":"2850_CR36","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/s41588-020-0653-y","volume":"52","author":"Z Ning","year":"2020","unstructured":"Ning Z, Pawitan Y, Shen X (2020) High-definition likelihood inference of genetic correlations across human complex traits. Nat Genet 52:859\u2013864. https:\/\/doi.org\/10.1038\/s41588-020-0653-y","journal-title":"Nat Genet"},{"key":"2850_CR37","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s12016-019-08756-7","volume":"58","author":"DD Odineal","year":"2020","unstructured":"Odineal DD, Gershwin ME (2020) The epidemiology and clinical manifestations of autoimmunity in selective IgA deficiency. Clin Rev Allergy Immun 58:107\u2013133","journal-title":"Clin Rev Allergy Immun"},{"issue":"3006\u20133021","key":"2850_CR38","volume":"184","author":"M Ota","year":"2021","unstructured":"Ota M, Nagafuchi Y, Hatano H, Ishigaki K, Terao C, Takeshima Y, Yanaoka H, Kobayashi S, Okubo M, Shirai H (2021) Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases. Cell 184(3006\u20133021):e3017","journal-title":"Cell"},{"key":"2850_CR39","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","volume":"26","author":"RJ Pruim","year":"2010","unstructured":"Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26:2336\u20132337. https:\/\/doi.org\/10.1093\/bioinformatics\/btq419","journal-title":"Bioinformatics"},{"key":"2850_CR40","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559\u2013575. https:\/\/doi.org\/10.1086\/519795","journal-title":"Am J Hum Genet"},{"key":"2850_CR41","unstructured":"Rasteiro, G.H.a.B.E.a.T.P.a.R. (2025). ieugwasr: Interface to the 'OpenGWAS' Database API. https:\/\/github.com\/MRCIEU\/ieugwasr."},{"key":"2850_CR42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009584","volume":"17","author":"D Ray","year":"2021","unstructured":"Ray D, Venkataraghavan S, Zhang W, Leslie EJ, Hetmanski JB, Weinberg SM, Murray JC, Marazita ML, Ruczinski I, Taub MA, Beaty TH (2021) Pleiotropy method reveals genetic overlap between orofacial clefts at multiple novel loci from GWAS of multi-ethnic trios. PLoS Genet 17:e1009584. https:\/\/doi.org\/10.1371\/journal.pgen.1009584","journal-title":"PLoS Genet"},{"key":"2850_CR43","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.4049\/jimmunol.1100857","volume":"187","author":"T Robinson","year":"2011","unstructured":"Robinson T, Kariuki SN, Franek BS, Kumabe M, Kumar AA, Badaracco M, Mikolaitis RA, Guerrero G, Utset TO, Drevlow BE et al (2011) Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-\u03b1 and serologic autoimmunity in lupus patients. J Immunol 187:1298\u20131303. https:\/\/doi.org\/10.4049\/jimmunol.1100857","journal-title":"J Immunol"},{"key":"2850_CR44","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/s41586-020-2436-0","volume":"584","author":"S Saevarsdottir","year":"2020","unstructured":"Saevarsdottir S, Olafsdottir TA, Ivarsdottir EV, Halldorsson GH, Gunnarsdottir K, Sigurdsson A, Johannesson A, Sigurdsson JK, Juliusdottir T, Lund SH et al (2020) FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease. Nature 584:619\u2013623. https:\/\/doi.org\/10.1038\/s41586-020-2436-0","journal-title":"Nature"},{"key":"2850_CR45","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s00439-005-0101-1","volume":"118","author":"AA Sch\u00e4ffer","year":"2006","unstructured":"Sch\u00e4ffer AA, Pfannstiel J, Webster AD, Plebani A, Hammarstr\u00f6m L, Grimbacher B (2006) Analysis of families with common variable immunodeficiency (CVID) and IgA deficiency suggests linkage of CVID to chromosome 16q. Hum Genet 118:725\u2013729. https:\/\/doi.org\/10.1007\/s00439-005-0101-1","journal-title":"Hum Genet"},{"issue":"1701\u20131715","key":"2850_CR46","volume":"175","author":"BJ Schmiedel","year":"2018","unstructured":"Schmiedel BJ, Singh D, Madrigal A, Valdovino-Gonzalez AG, White BM, Zapardiel-Gonzalo J, Ha B, Altay G, Greenbaum JA, McVicker G (2018) Impact of genetic polymorphisms on human immune cell gene expression. Cell 175(1701\u20131715):e1716","journal-title":"Cell"},{"key":"2850_CR47","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.clim.2018.09.008","volume":"197","author":"N Shulzhenko","year":"2018","unstructured":"Shulzhenko N, Dong X, Vyshenska D, Greer RL, Gurung M, Vasquez-Perez S, Peremyslova E, Sosnovtsev S, Quezado M, Yao M et al (2018) CVID enteropathy is characterized by exceeding low mucosal IgA levels and interferon-driven inflammation possibly related to the presence of a pathobiont. Clin Immunol 197:139\u2013153. https:\/\/doi.org\/10.1016\/j.clim.2018.09.008","journal-title":"Clin Immunol"},{"key":"2850_CR48","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.autrev.2013.10.005","volume":"13","author":"K Singh","year":"2014","unstructured":"Singh K, Chang C, Gershwin ME (2014) IgA deficiency and autoimmunity. Autoimmun Rev 13:163\u2013177. https:\/\/doi.org\/10.1016\/j.autrev.2013.10.005","journal-title":"Autoimmun Rev"},{"key":"2850_CR49","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00016","volume":"10","author":"NG Skene","year":"2016","unstructured":"Skene NG, Grant SG (2016) Identification of vulnerable cell types in major brain disorders using single cell transcriptomes and expression weighted cell type enrichment. Front Neurosci 10:16. https:\/\/doi.org\/10.3389\/fnins.2016.00016","journal-title":"Front Neurosci"},{"key":"2850_CR50","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1038\/s41423-020-00626-z","volume":"18","author":"G Sogkas","year":"2021","unstructured":"Sogkas G, Atschekzei F, Adriawan IR, Dubrowinskaja N, Witte T, Schmidt RE (2021) Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity. Cell Mole Immunol 18:1122\u20131140. https:\/\/doi.org\/10.1038\/s41423-020-00626-z","journal-title":"Cell Mole Immunol"},{"key":"2850_CR51","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","volume":"622","author":"BB Sun","year":"2023","unstructured":"Sun BB, Chiou J, Traylor M, Benner C, Hsu Y-H, Richardson TG, Surendran P, Mahajan A, Robins C, Vasquez-Grinnell SG et al (2023) Plasma proteomic associations with genetics and health in the UK Biobank. Nature 622:329\u2013338. https:\/\/doi.org\/10.1038\/s41586-023-06592-6","journal-title":"Nature"},{"key":"2850_CR52","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.4049\/jimmunol.2400344","volume":"213","author":"JP Taylor","year":"2024","unstructured":"Taylor JP, Blum SI, Graffeo HC, Shang Q, Qiu S, Green TJ, Botta D, Lund FE, Tse HM (2024) The type 1 diabetes-associated single nucleotide polymorphism rs1990760 in IFIH1 Is associated with increased basal type I IFNs and IFN-stimulated Gene expression. J Immunol 213:1415\u20131428. https:\/\/doi.org\/10.4049\/jimmunol.2400344","journal-title":"J Immunol"},{"key":"2850_CR53","doi-asserted-by":"publisher","first-page":"R112","DOI":"10.1186\/ar2771","volume":"11","author":"DL Thibault","year":"2009","unstructured":"Thibault DL, Graham KL, Lee LY, Balboni I, Hertzog PJ, Utz PJ (2009) Type I interferon receptor controls B-cell expression of nucleic acid-sensing Toll-like receptors and autoantibody production in a murine model of lupus. Arthritis Res Ther 11:R112. https:\/\/doi.org\/10.1186\/ar2771","journal-title":"Arthritis Res Ther"},{"key":"2850_CR54","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1038\/ng.998","volume":"43","author":"G Trynka","year":"2011","unstructured":"Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, Szperl A, Bakker SF, Bardella MT, Bhaw-Rosun L, Castillejo G (2011) Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet 43:1193\u20131201","journal-title":"Nat Genet"},{"key":"2850_CR55","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/ng.2467","volume":"44","author":"LC Tsoi","year":"2012","unstructured":"Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, Ding J, Li Y, Tejasvi T, Gudjonsson JE (2012) Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nature Genet 44:1341\u20131348","journal-title":"Nature Genet"},{"key":"2850_CR56","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41588-017-0009-4","volume":"50","author":"P Turley","year":"2018","unstructured":"Turley P, Walters RK, Maghzian O, Okbay A, Lee JJ, Fontana MA, Nguyen-Viet TA, Wedow R, Zacher M, Furlotte NA et al (2018) Multi-trait analysis of genome-wide association summary statistics using MTAG. Nat Genet 50:229\u2013237. https:\/\/doi.org\/10.1038\/s41588-017-0009-4","journal-title":"Nat Genet"},{"key":"2850_CR57","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck M, Chen C-Y, Neale B, Do R (2018) Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet 50:693\u2013698. https:\/\/doi.org\/10.1038\/s41588-018-0099-7","journal-title":"Nat Genet"},{"key":"2850_CR58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/6043710","volume":"2018","author":"R Villanueva-Romero","year":"2018","unstructured":"Villanueva-Romero R, Guti\u00e9rrez-Ca\u00f1as I, Carri\u00f3n M, P\u00e9rez-Garc\u00eda S, Seoane IV, Mart\u00ednez C, Gomariz RP, Juarranz Y (2018) The anti-inflammatory mediator, vasoactive intestinal peptide, modulates the differentiation and function of th subsets in rheumatoid arthritis. J Immunol Res 2018:1. https:\/\/doi.org\/10.1155\/2018\/6043710","journal-title":"J Immunol Res"},{"key":"2850_CR59","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41588-021-00913-z","volume":"53","author":"U V\u00f5sa","year":"2021","unstructured":"V\u00f5sa U, Claringbould A, Westra H-J, Bonder MJ, Deelen P, Zeng B, Kirsten H, Saha A, Kreuzhuber R, Yazar S (2021) Large-scale cis-and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet 53:1300\u20131310","journal-title":"Nat Genet"},{"key":"2850_CR60","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13223-023-00826-y","volume":"19","author":"A Vosughimotlagh","year":"2023","unstructured":"Vosughimotlagh A, Rasouli SE, Rafiemanesh H, Safarirad M, Sharifinejad N, Madanipour A, Dos Santos Vilela MM, Heropolita\u0144ska-Pliszka E, Azizi G (2023) Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis. Allergy Asthma Clin Immunol 19:75. https:\/\/doi.org\/10.1186\/s13223-023-00826-y","journal-title":"Allergy Asthma Clin Immunol"},{"key":"2850_CR61","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.2119\/molmed.2011.00195","volume":"17","author":"N Wang","year":"2011","unstructured":"Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, Rantap\u00e4\u00e4-Dahlqvist S, Elvin K, Truedsson L, Andersson BA et al (2011) Selective IgA deficiency in autoimmune diseases. Mol Med 17:1383\u20131396. https:\/\/doi.org\/10.2119\/molmed.2011.00195","journal-title":"Mol Med"},{"key":"2850_CR62","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/s41467-021-21049-y","volume":"12","author":"Y-F Wang","year":"2021","unstructured":"Wang Y-F, Zhang Y, Lin Z, Zhang H, Wang T-Y, Cao Y, Morris DL, Sheng Y, Yin X, Zhong S-L (2021) Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups. Nat Commun 12:772","journal-title":"Nat Commun"},{"key":"2850_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110367","volume":"268","author":"FQ Wang","year":"2024","unstructured":"Wang FQ, Dang X, Yang W (2024) Transcriptomic studies unravel the molecular and cellular complexity of systemic lupus erythematosus: a review. Clin Immunol 268:110367. https:\/\/doi.org\/10.1016\/j.clim.2024.110367","journal-title":"Clin Immunol"},{"key":"2850_CR64","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","volume":"8","author":"K Watanabe","year":"2017","unstructured":"Watanabe K, Taskesen E, van Bochoven A, Posthuma D (2017) Functional mapping and annotation of genetic associations with FUMA. Nat Commun 8:1826. https:\/\/doi.org\/10.1038\/s41467-017-01261-5","journal-title":"Nat Commun"},{"key":"2850_CR65","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/s41588-022-01017-y","volume":"54","author":"J Werme","year":"2022","unstructured":"Werme J, van der Sluis S, Posthuma D, de Leeuw CA (2022) An integrated framework for local genetic correlation analysis. Nat Genet 54:274\u2013282. https:\/\/doi.org\/10.1038\/s41588-022-01017-y","journal-title":"Nat Genet"},{"key":"2850_CR66","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer CJ, Li Y, Abecasis GR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26:2190\u20132191. https:\/\/doi.org\/10.1093\/bioinformatics\/btq340","journal-title":"Bioinformatics"},{"key":"2850_CR67","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3041","volume":"376","author":"S Yazar","year":"2022","unstructured":"Yazar S, Alquicira-Hernandez J, Wing K, Senabouth A, Gordon MG, Andersen S, Lu Q, Rowson A, Taylor TR, Clarke L (2022) Single-cell eQTL mapping identifies cell type\u2013specific genetic control of autoimmune disease. Science 376:eabf3041","journal-title":"Science"},{"key":"2850_CR68","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s10875-009-9357-x","volume":"30","author":"L Yel","year":"2010","unstructured":"Yel L (2010) Selective IgA deficiency. J Clin Immunol 30:10\u201316. https:\/\/doi.org\/10.1007\/s10875-009-9357-x","journal-title":"J Clin Immunol"},{"key":"2850_CR69","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang L-G, Han Y, He Q-Y (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. Omics 16:284\u2013287","journal-title":"Omics"},{"key":"2850_CR70","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221080","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Morris R, Brown GJ, Lorenzo AMD, Meng X, Kershaw NJ, Kiridena P, Burgio G, Gross S, Cappello JY et al (2024) Rare SH2B3 coding variants in lupus patients impair B cell tolerance and predispose to autoimmunity. J Exp Med. https:\/\/doi.org\/10.1084\/jem.20221080","journal-title":"J Exp Med"},{"key":"2850_CR71","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02043-4","volume":"10","author":"X Zhou","year":"2025","unstructured":"Zhou X, Wu Y, Zhu Z, Lu C, Zhang C, Zeng L, Xie F, Zhang L, Zhou F (2025) Mucosal immune response in biology, disease prevention and treatment. Sig Trans Targeted Therapy 10:7. https:\/\/doi.org\/10.1038\/s41392-024-02043-4","journal-title":"Sig Trans Targeted Therapy"}],"container-title":["Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-026-02850-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00439-026-02850-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-026-02850-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T08:15:01Z","timestamp":1782116101000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00439-026-02850-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["2850"],"URL":"https:\/\/doi.org\/10.1007\/s00439-026-02850-5","relation":{},"ISSN":["0340-6717","1432-1203"],"issn-type":[{"value":"0340-6717","type":"print"},{"value":"1432-1203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]},"assertion":[{"value":"16 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"53"}}