A locus on chromosome 1p36 is associated with thyrotropin and thyroid function as identified by genome-wide association study.

Thyroid hormones are key regulators of cellular growth, development, and metabolism, and thyroid disorders are a common cause of ill health in the community. Circulating concentrations of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) have a strong heritable component and are thought to be under polygenic control, but the genes responsible are mostly unknown. In order to identify genetic loci associated with these metabolic phenotypes, we performed a genome-wide association study of 2,120,505 SNPs in 2014 female twins from the TwinsUK study and found a significant association between rs10917469 on chromosome 1p36.13 and serum TSH (p = 3.2 × 10(-8)). The association of rs10917469 with serum TSH was replicated (p = 2.0 × 10(-4)) in an independent community-based sample of 1154 participants in the Busselton Health Study. This SNP is located near CAPZB, which might be a regulator of TSH secretion and thus of pituitary-thyroid axis function. Twenty-nine percent of white individuals carry the variant, and the difference in mean TSH concentrations between wild-type individuals and those homozygous for the minor G allele was 0.5 mU/l, which is likely to be clinically relevant. We also provide evidence of suggestive association (p < 5.0 × 10(-6)) of other SNPs with serum TSH, free T4, and free T3 concentrations, and these SNPs might be good targets for further studies. These results advance understanding of the genetic basis of pituitary-thyroid axis function and metabolic regulation.

A comparative study between corresponding structural geometric variables using 2 commonly implemented hip structural analysis algorithms applied to dual-energy X-ray absorptiometry images.

Hip structural analysis (HSA) has been developed over 20 yr, applied extensively in research, and has demonstrated useful outcomes associating bone structural geometry with bone fragility (research-HSA or r-HSA). In 2007, Hologic Inc. (Bedford, MA) incorporated HSA with some modifications as an option for Hologic dual-energy X-ray absorptiometry (DXA) scanners (clinical HSA or c-HSA). This brought HSA from the research environment into the clinical environment. This article reports a comparison of r-HSA and c-HSA implementations using DXA scans from a group of 191 females. Bland-Altman plots at the narrow-neck (NN) HSA region indicated higher r-HSA areal bone mineral density (mean difference: 0.27 g/cm(2); 21.7% [of mean]); cross-sectional area (0.63 cm(2); 18.7%); cross-sectional moment of inertia (0.26 cm(4); 11.1%), and section modulus (0.22 cm(3); 14.5%) compared with c-HSA. The converse was observed for NN subperiosteal width (-0.09 cm; 3.1%). High linear correlations (r(2) > 0.81) were found between r-HSA and c-HSA NN structural geometric outcomes, with the exception of neck shaft angle (r(2) > 0.47). As differences were significant (p < 0.001), slopes and intercepts are provided to enable linear transformations from r-HSA to corresponding c-HSA structural geometric data.