Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's diseaseDepartment of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Department of Endocrinology, Metabolism and Diabetes Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes Karolinska University Hospital, Stockholm, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
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2016 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 280, no 6, p. 595-608Article in journal (Refereed) Published
Abstract [en]
BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.
METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.
RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10-15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.
CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
Place, publisher, year, edition, pages
Wiley-Blackwell, 2016. Vol. 280, no 6, p. 595-608
Keywords [en]
Addison Disease, BACH2 protein, genetic, genetic association studies, genetic predisposition to disease, human, polymorphism
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-110417DOI: 10.1111/joim.12569ISI: 000388573300007PubMedID: 27807919Scopus ID: 2-s2.0-84995811839OAI: oai:DiVA.org:oru-110417DiVA, id: diva2:1820586
Funder
AstraZenecaSwedish Research CouncilSwedish Rheumatism AssociationStiftelsen Konung Gustaf V:s 80-årsfondNovo Nordisk FoundationRagnar Söderbergs stiftelseTorsten Söderbergs stiftelse
Note
Funding Agencies:
AstraZeneca
Swedish Research Council
KAW Foundation
Swedish Reumatism Foundation
King Gustaf V′s 80-year Foundation
Novo Nordisk Foundation
Torsten and Ragnar Söderberg's Foundations
2023-12-182023-12-182023-12-19Bibliographically approved