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Pooled genome wide association detects association upstream of FCRL3 with Graves' disease


Khong, JJ and Burdon, KP and Lu, Y and Laurie, K and Leonardos, L and Baird, PN and Sahebjada, S and Walsh, JP and Gajdatsy, A and Ebeling, PR and Hamblin, PS and Wong, R and Forehan, SP and Fourlanos, S and Roberts, AP and Doogue, M and Selva, D and Montgomery, GW and Macgregor, S and Craig, JE, Pooled genome wide association detects association upstream of FCRL3 with Graves' disease, BMC Genomics, 17, (1) Article 939. ISSN 1471-2164 (2016) [Refereed Article]


Copyright Statement

Copyright 2016 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1186/s12864-016-3276-z


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.

Item Details

Item Type:Refereed Article
Keywords:Genome-wide association study, Gravesí disease, Pooled blood
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:112651
Year Published:2016
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-11-22
Last Modified:2022-08-29
Downloads:162 View Download Statistics

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