D Eriksson1,2, M Bianchi3, N Landegren1,4, J Nordin3, F Dalin1,4, A Mathioudaki3, G N Eriksson5, L Hultin-Rosenberg3, J Dahlqvist3, H Zetterqvist3,4, Å Karlsson3, Å Hallgren1,4, F H G Farias3, E Murén3, K M Ahlgren4, A Lobell4, G Andersson6, K Tandre4, S R Dahlqvist7, P Söderkvist8, L Rönnblom4, A-L Hulting5, J Wahlberg9, O Ekwall10,11, P Dahlqvist7, J R S Meadows3, S Bensing2,5, K Lindblad-Toh3,12, O Kämpe1,2,4, G R Pielberg3. 1. Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 2. Department of Endocrinology, Metabolism and Diabetes Karolinska University Hospital, Stockholm, Sweden. 3. Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. 4. Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 5. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 6. Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden. 7. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 8. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 9. Department of Endocrinology, Department of Medical and Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 10. Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 11. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 12. Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Abstract
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.
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.
Authors: Mika Moriwaki; Barry Moore; Timothy Mosbruger; Deborah W Neklason; Mark Yandell; Lynn B Jorde; Corrine K Welt Journal: J Endocr Soc Date: 2017-02-07
Authors: Jakob Skov; Jonas Höijer; Patrik K E Magnusson; Jonas F Ludvigsson; Olle Kämpe; Sophie Bensing Journal: Endocrine Date: 2017-10-16 Impact factor: 3.633
Authors: Argyri Mathioudaki; Viktor Ljungström; Malin Melin; Maja Louise Arendt; Jessika Nordin; Åsa Karlsson; Eva Murén; Pushpa Saksena; Jennifer R S Meadows; Voichita D Marinescu; Tobias Sjöblom; Kerstin Lindblad-Toh Journal: Sci Rep Date: 2020-11-09 Impact factor: 4.379
Authors: Johanna K Sandling; Pascal Pucholt; Lina Hultin Rosenberg; Fabiana H G Farias; Sergey V Kozyrev; Maija-Leena Eloranta; Andrei Alexsson; Matteo Bianchi; Leonid Padyukov; Christine Bengtsson; Roland Jonsson; Roald Omdal; Benedicte A Lie; Laura Massarenti; Rudi Steffensen; Marianne A Jakobsen; Søren T Lillevang; Karoline Lerang; Øyvind Molberg; Anne Voss; Anne Troldborg; Søren Jacobsen; Ann-Christine Syvänen; Andreas Jönsen; Iva Gunnarsson; Elisabet Svenungsson; Solbritt Rantapää-Dahlqvist; Anders A Bengtsson; Christopher Sjöwall; Dag Leonard; Kerstin Lindblad-Toh; Lars Rönnblom Journal: Ann Rheum Dis Date: 2020-10-09 Impact factor: 19.103