Pooled Genome Wide Association Detects Association Upstream of FCRL3 with Graves' Disease

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2016 Nov 20

PMID 27863461

Citations 9

Authors

Jwu Jin Khong

Kathryn P Burdon

Yi Lu

Kate Laurie

Lefta Leonardos

Paul N Baird

Srujana Sahebjada

John P Walsh

Adam Gajdatsy

Peter R Ebeling

Peter Shane Hamblin

Rosemary Wong

Simon P Forehan

Spiros Fourlanos

Anthony P Roberts

Matthew Doogue

Dinesh Selva

Grant W Montgomery

Stuart Macgregor

Jamie E Craig

Affiliations

Soon will be listed here.

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). 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. 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.

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