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Title: Pooled genome wide association detects association upstream of FCRL3 with Graves' disease
Austin Authors: Khong, Jwu Jin;Burdon, Kathryn P;Lu, Yi;Laurie, Kate;Leonardos, Lefta;Baird, Paul N;Sahebjada, Srujana;Walsh, John P;Gajdatsy, Adam;Ebeling, Peter R;Hamblin, Peter Shane;Wong, Rosemary;Forehan, Simon P;Fourlanos, Spiros;Roberts, Anthony P;Doogue, Matthew;Selva, Dinesh;Montgomery, Grant W;Macgregor, Stuart;Craig, Jamie E
Affiliation: Austin Health, Heidelberg, Victoria, Australia
Melbourne Medical School Western Campus, Department of Medicine, University of Melbourne, Sunshine Hospital, St Albans, Victoria, Australia
Orbital, Plastics and Lacrimal Unit, The Royal Victorian Eye and Ear Hospital, Heidelberg, VIC, Australia
Department of Ophthalmology and Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
Statistical Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Herston, Queensland, Australia
Department of Ophthalmology, Flinders University of South Australia, Bedford Park, South Australia, Australia
Department of Surgery, Centre for Eye Research Australia and Ophthalmology, University of Melbourne, East Melbourne, Victoria, Australia
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia
Centre for Ophthalmology and Visual Sciences, University of Western Australia, Western Australia, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
Department of Endocrinology and Diabetes, Western Health, St Albans, Victoria, Australia
Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia
Department of Endocrinology, The Royal Adelaide Hospital, Adelaide, South Australia, Australia
Department of Medicine, University of Otago, Christchurch, New Zealand
South Australian Institute of Ophthalmology, University of Adelaide, South Australia, Australia
Molecular Epidemiology, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Herston, Queensland, Australia
Issue Date: 18-Nov-2016
Date: 2016-11-18
Publication information: BMC Genomics 2016; 17(1): 939
Abstract: BACKGROUND: Graves' disease is an autoimmune thyroid disease of complex inheritance. Multiple genetic susceptibility loci are thought to be involved in Graves' disease and it is therefore likely that these can be identified by genome wide association studies. This study aimed to determine if a genome wide association study, using a pooling methodology, could detect genomic loci associated with Graves' disease. RESULTS: Nineteen of the top ranking single nucleotide polymorphisms including HLA-DQA1 and C6orf10, were clustered within the Major Histo-compatibility Complex region on chromosome 6p21, with rs1613056 reaching genome wide significance (p = 5 × 10-8). Technical validation of top ranking non-Major Histo-compatablity complex single nucleotide polymorphisms with individual genotyping in the discovery cohort revealed four single nucleotide polymorphisms with p ≤ 10-4. Rs17676303 on chromosome 1q23.1, located upstream of FCRL3, showed evidence of association with Graves' disease across the discovery, replication and combined cohorts. A second single nucleotide polymorphism rs9644119 downstream of DPYSL2 showed some evidence of association supported by finding in the replication cohort that warrants further study. CONCLUSIONS: Pooled genome wide association study identified a genetic variant upstream of FCRL3 as a susceptibility locus for Graves' disease in addition to those identified in the Major Histo-compatibility Complex. A second locus downstream of DPYSL2 is potentially a novel genetic variant in Graves' disease that requires further confirmation.
DOI: 10.1186/s12864-016-3276-z
Journal: BMC Genomics
PubMed URL:
Type: Journal Article
Subjects: Genome-wide association study
Pooled blood
Appears in Collections:Journal articles

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