Skewed X chromosome inactivation and female preponderance in autoimmune thyroid disease: an association study and meta-analysis

Simmonds, M. J., Kavvoura, F. K., Brand, O. J. , Newby, P. R., Jackson, L. E., Hargreaves, C. E., Franklyn, J. A. and Gough, S. C. L. (2014) Skewed X chromosome inactivation and female preponderance in autoimmune thyroid disease: an association study and meta-analysis. Journal of Clinical Endocrinology and Metabolism, 99 (1). ISSN 0021-972X

Full content URL: http://dx.doi.org/10.1210/jc.2013-2667

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Abstract

CONTEXT:

A number of small data sets have suggested a potential role for skewed X chromosome activation (XCI), away from the expected 50:50 parent of origin ratio, as an explanation for the strong female preponderance seen in the common autoimmune thyroid diseases (AITD), Graves' disease (GD), and Hashimoto's thyroiditis (HT).

OBJECTIVE:

The objective of the study was to confirm a role for XCI skewing as a potential explanation for the strong female preponderance seen in AITD.

DESIGN:

The design of the study was to screen XCI in the largest GD, HT, and control case-control cohort and family cohort to date and undertake a meta-analysis of previous AITD XCI reports.

SETTING:

The study was conducted at a research laboratory.

PATIENTS:

Three hundred and nine GD, 490 HT, and 325 female UK Caucasians controls, 273 UK Caucasian GD families, and a meta-analysis of 454 GD, 673 HT, and 643 female Caucasian controls were included in the study.

MAIN OUTCOME MEASURES:

Case-control and family-based association studies and meta-analysis were measured.

RESULTS:

Skewed XCI was observed with GD [odds ratio (OR) 2.17 [95% confidence interval (CI) 1.43-3.30], P=2.1×10(-4)] and a trend toward skewing with HT (P=.08) compared with the control cohort. A meta-analysis of our UK data and that of four previous non-UK Caucasian studies confirmed significant skewing of XCI with GD [OR 2.54 (95% CI 1.58-4.10), P=1.0×10(-4), I2=30.2%] and HT [OR 2.40 (95% CI 1.10-5.26), P=.03, I2=74.3%].

CONCLUSIONS:

Convincing evidence exists to support a role for skewed XCI in female subjects with AITD, which may, in part, explain the strong female preponderance observed in this disease.

Keywords:X chromosome, graves disease, Autoimmune Diseases, Genetics, Female preponderance, JCOpen
Subjects:C Biological Sciences > C431 Medical Genetics
Divisions:College of Science > School of Life Sciences
ID Code:22243
Deposited On:15 Feb 2016 09:57

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