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Association of Polymorphisms in MACRO Domain Containing 2 With Thyroid-Associated Orbitopathy


Khong, JJ and Burdon, KP and Lu, Y and Leonardos, L and Laurie, KJ and Walsh, JP and Gajdatsy, AD and Ebeling, PR and McNab, AA and Hardy, TG and Stawell, RJ and Davis, GJ and Selva, D and Tsirbas, A and Montgomery, GW and Macgregor, S and Craig, JE, Association of Polymorphisms in MACRO Domain Containing 2 With Thyroid-Associated Orbitopathy, Investigative Ophthalmology and Visual Science (IOVS), 57, (7) pp. 3129-3137. ISSN 0146-0404 (2016) [Refereed Article]


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Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

DOI: doi:10.1167/iovs.15-18797


PURPOSE: Thyroid-associated orbitopathy (TO) is an autoimmune-mediated orbital inflammation that can lead to disfigurement and blindness. Multiple genetic loci have been associated with Graves' disease, but the genetic basis for TO is largely unknown. This study aimed to identify loci associated with TO in individuals with Graves' disease, using a genome-wide association scan (GWAS) for the first time to our knowledge in TO.

METHODS: Genome-wide association scan was performed on pooled DNA from an Australian Caucasian discovery cohort of 265 participants with Graves' disease and TO (cases) and 147 patients with Graves' disease without TO (controls). Top-ranked single nucleotide polymorphisms (SNPs) then were genotyped in individual DNA samples from the discovery cohort, and two replication cohorts totaling 584 cases and 367 controls.

RESULTS: In the GWAS of pooled DNA samples, several SNPs showed suggestive association with TO at genome-wide P ≤ 10-6; rs953128 located on chr10q21.1, rs2867161 on chr7q11.22, rs13360861 on chr5q12.3, rs7636326 on chr3q26.2, rs10266576 on chr 7q11.22, rs60457622 on chr3q23, and rs6110809 on chr20p12.1. However, the only SNP consistently associated with TO on individual genotyping in the discovery and replication cohorts was rs6110809, located within MACROD2 on chromosome 20p12.1. On combined analysis of discovery and replication cohorts, the minor A allele of rs6110809 was more frequent in TO than in Graves' disease controls without TO (P = 4.35 10-5; odds ratio [OR] = 1.77; 95% confidence interval [CI], 1.35-2.32) after adjusting for age, sex, duration of Graves' disease, and smoking.

CONCLUSIONS: In patients with Graves' disease, a common genetic variant in MACROD2 may increase susceptibility for thyroid-associated orbitopathy. This association now requires confirmation in additional independent cohorts.

Item Details

Item Type:Refereed Article
Keywords:genome-wide association study, genotyping, thyroid-associated orbitopathy
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:109533
Year Published:2016
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-06-21
Last Modified:2017-11-06
Downloads:206 View Download Statistics

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