title: Pooled genome wide association detects association upstream of FCRL3 with Graves' disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Melbourne Medical School Western Campus, Department of Medicine, University of Melbourne, Sunshine Hospital, 176 Furlong Road, St Albans, VIC, 3021, Australia. jwujinkhong@gmail.com.|Orbital, Plastics and Lacrimal Unit, The Royal Victorian Eye and Ear Hospital, Heidelberg, VIC, Australia. jwujinkhong@gmail.com.|Department of Ophthalmology and Department of Surgery, University of Melbourne, Austin Health, Heidelberg, VIC, Australia. jwujinkhong@gmail.com.
authors.forename: Jwu Jin
authors.identifier: 0000-0002-2660-4668
authors.initials: JJ
authors.lastname: Khong
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.affiliation: Statistical Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Ophthalmology, Flinders University of South Australia, Bedford Park, South Australia, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Laurie
authors.affiliation: Department of Ophthalmology, Flinders University of South Australia, Bedford Park, South Australia, Australia.
authors.forename: Lefta
authors.initials: L
authors.lastname: Leonardos
authors.affiliation: Department of Surgery, Centre for Eye Research Australia and Ophthalmology, University of Melbourne, East Melbourne, VIC, Australia.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.affiliation: Department of Surgery, Centre for Eye Research Australia and Ophthalmology, University of Melbourne, East Melbourne, VIC, Australia.
authors.forename: Srujana
authors.initials: S
authors.lastname: Sahebjada
authors.affiliation: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.|School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA, Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
authors.affiliation: Centre for Ophthalmology and Visual Sciences, University of Western Australia, Western Australia, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Gajdatsy
authors.affiliation: Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
authors.affiliation: Melbourne Medical School Western Campus, Department of Medicine, University of Melbourne, Sunshine Hospital, 176 Furlong Road, St Albans, VIC, 3021, Australia.|Department of Endocrinology and Diabetes, Western Health, St Albans, VIC, Australia.
authors.forename: Peter Shane
authors.initials: PS
authors.lastname: Hamblin
authors.affiliation: Department of Endocrinology and Diabetes, Western Health, St Albans, VIC, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Wong
authors.affiliation: Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Forehan
authors.affiliation: Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: Spiros
authors.initials: S
authors.lastname: Fourlanos
authors.affiliation: Department of Endocrinology, The Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Roberts
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Matthew
authors.initials: M
authors.lastname: Doogue
authors.affiliation: South Australian Institute of Ophthalmology, University of Adelaide, South Australia, Australia.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Selva
authors.affiliation: Molecular Epidemiology, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Statistical Genetics, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Herston, QLD, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.affiliation: Department of Ophthalmology, Flinders University of South Australia, Bedford Park, South Australia, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*
chemical_list: C457775:FCRL3 protein, human; D011971:Receptors, Immunologic
keywords: Genome-wide association study; Graves’ disease; Pooled blood