September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Association of polymorphisms in MACRO domain containing 2 with thyroid orbitopathy
Author Affiliations & Notes
  • Jwu Jin Khong
    Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Jwu Jin Khong, None
  • Footnotes
    Support  Ophthalmic Research Institute of Australia, National Health and Medical Research Council of Australia
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6570. doi:
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      Jwu Jin Khong; Association of polymorphisms in MACRO domain containing 2 with thyroid orbitopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6570.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Thyroid 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 in TO.

Methods : GWAS 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) were then 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 within PCDH15 on chr10q21.1, rs2867161 on chr7q11.22, rs13360861 on chr5q12.3, rs7636326 within SLC7A14 on chr3q26.2, rs10266576 on chr 7q11.22, rs60457622 on chr3q23, and rs6110809 on chr20p12.1 within MACROD2. 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=2.06x10-5, OR=1.85, 95% CI 1.39-2.45) after adjusting for age, sex and smoking.

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

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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