DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Thyroid function. The EFO term thyroid function was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: thyroid function

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

R Rawal, A Teumer, H Völzke, H Wallaschofski, T Ittermann, BO Åsvold, T Bjøro, KH Greiser, D Tiller, K Werdan, HE Meyer zu Schwabedissen, A Doering, T Illig, C Gieger, C Meisinger, G Homuth

TITLE:

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

JOURNAL:

Human molecular genetics Jul 2012, Vol 21, pp. 3275-82

ABSTRACT:

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. PUBMED: 22494929
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