Preliminary study of genome-wide association identified novel susceptibility genes for thyroid-related hormones in Chinese population

Background Thyroid hormones are critical regulators of metabolism, development and growth in mammals. However, the genetic association of thyroid-related hormones in the Chinese Han population is not fully understood. Objective We aimed to identify the genetic loci associated with circulating thyroid-related hormones concentrations in the healthy Chinese Han population. Methods Genotyping was performed in 124 individuals using Applied Biosystems™ Axiom™ PMDA, and 796,288 single nucleotide polymorphisms (SNPs) were available for the GWAS analysis. For replication, eleven SNPs were selected as candidate loci for genotyping by Agena MassARRAY platform in additional samples (313 subjects). The values of p < 5 × 10 − 6 suggest a suggestively significant genome-wide association with circulating thyroid-related hormones concentrations. Results We identified that rs11178277 ( PTPRB , p = 4.88 × 10 − 07 ) and rs7320337 ( LMO7DN - KCTD12 , p = 1.22 × 10 − 06 ) were associated with serum FT3 level. Three SNPs (rs4850041 in LOC105373394 - LINC01249 : p = 3.55 × 10 − 06 , rs6867291 in LINC02208 : p = 2.40 × 10 − 06 and rs79508321 in WWOX : p = 3.35 × 10 − 06 ) were related to circulating T3 level. Rs12474167 ( LOC105373394 - LINC01249 , p = 1.65 × 10 − 06 ) and rs1864553 ( IWS1 , p = 2.00 × 10 − 06 ) were associated with circulating T4 concentration. The association with TGA concentration was for rs17163542 in DISP1 ( p = 3.46 × 10 − 06 ) and rs12601151 in NOG - C17orf67 ( p = 2.72 × 10 − 07 ). Two genome-level significant SNPs (rs2114707 in LINC01314 , p = 1.69 × 10 − 06 and rs12601151, p = 1.41 × 10 − 07 ) associated with serum TMA concentration were identified. Moreover, rs6083269 ( CST1 - CST2 , p = 3.36 × 10 − 06 ) was a significant locus for circulating TSH level. In replication, rs12601151 in NOG - C17orf67 was still associated with serum TGA level ( p = 0.012). Conclusions The GWAS reported 11 new suggestively significant loci associated with circulating thyroid-related hormones levels among the Chinese Han population. These findings represented suggestively biological candidates for circulating thyroid-related hormones levels and provided new insights into the mechanisms of regulating serum TGA concentration.