A genome-wide association study yields five novel thyroid cancer risk loci

Abstract

The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with P_combined<3 × 10^-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10^-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.

Figure 1. A Manhattan plot of the combined thyroid cancer GWAS results.

The Manhattan plot shows 7.1 million variants with high imputation information score (info≥0.90) from the thyroid cancer meta-analysis of GWAS data from 3,001 patients and 287,550 controls from five study groups of European descent coming from Iceland, the Netherlands, Spain and the USA. Shown are negative log₁₀-transformed P values over 22 autosomes. Previously published risk loci are in black and risk loci reported in current study are in red.