Journal Article

Meta-analysis of two genome-wide association studies identifies four genetic loci associated with thyroid function

Rajesh Rawal, Alexander Teumer, Henry Völzke, Henri Wallaschofski, Till Ittermann, Bjørn O. Åsvold, Trine Bjøro, Karin H. Greiser, Daniel Tiller, Karl Werdan, Henriette E. Meyer zu Schwabedissen, Angela Doering, Thomas Illig, Christian Gieger, Christa Meisinger and Georg Homuth

in Human Molecular Genetics

Volume 21, issue 14, pages 3275-3282
Published in print July 2012 | ISSN: 0964-6906
Published online April 2012 | e-ISSN: 1460-2083 | DOI:
Meta-analysis of two genome-wide association studies identifies four genetic loci associated with thyroid function

Show Summary Details


Thyroid hormones play key roles in cellular growth, development and metabolism. Although there is a strong genetic influence on thyroid hormone levels, the genes involved are widely unknown. The levels of circulating thyroid hormones are tightly regulated by thyrotropin (TSH), which also represents the most important diagnostic marker for thyroid function. Therefore, in order to identify genetic loci associated with TSH levels, we performed a discovery meta-analysis of two genome-wide association studies including two cohorts from Germany, KORA (n = 1287) and SHIP (n = 2449), resulting in a total sample size of 3736. Four genetic loci at 5q13.3, 1p36, 16q23 and 4q31 were associated with serum TSH levels. The lead single-nucleotide polymorphisms of these four loci were located within PDE8B encoding phosphodiesterase 8B, upstream of CAPZB that encodes the β-subunit of the barbed-end F-actin-binding protein, in a former ‘gene desert’ that was recently demonstrated to encode a functional gene (LOC440389) associated with thyroid volume, and upstream of NR3C2 encoding the mineralocorticoid receptor. The latter association for the first time suggests the modulation of thyroid function by mineral corticoids. All four loci were replicated in three additional cohorts: the HUNT study from Norway (n = 1487) and the two German studies CARLA (CARLA, n = 1357) and SHIP-TREND (n = 883). Together, these four quantitative trait loci accounted for ∼3.3% of the variance in TSH serum levels. These results contribute to our understanding of genetic factors and physiological mechanisms mediating thyroid function.

Journal Article.  5243 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.