ArticleProceedings of the National Academy of Sciences of the United States of America2015
Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 3 of them syntheses that pooled it.
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Who cites it
58 citing papers in PubMed, 3 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome.Journal of the American Society of Nephrology : JASN · 2018Pooled it
- rs965513 polymorphism as a common risk marker is associated with papillary thyroid cancer.Oncotarget · 2016Pooled it
- Early and late RNA eQTL are driven by different genetic mechanisms.Nature communications · 2026Article
- The FOXE1 rs965513 polymorphism: a pleiotropic risk locus associated with thyroid function, BRAFScientific reports · 2026Article
- High-resolution promoter interaction analysis implicates genes involved in the activation of Type 3 Innate Lymphoid Cells in autoimmune disease risk.bioRxiv : the preprint server for biology · 2026Article
- An evolving understanding of multiple causal variants underlying genetic association signals.American journal of human genetics · 2025Review
- Analyzing super-enhancer temporal dynamics reveals potential critical enhancers and their gene regulatory networks underlying skeletal muscle development.Genome research · 2024Article
- Article
- Role of toll-like receptor in the pathogenesis of oral cancer.Cell biochemistry and biophysics · 2024Review
- Identification of GermlineInternational journal of molecular sciences · 2024Article
- Radiation-Related Thyroid Cancer.Endocrine reviews · 2024Review
- Reduced expression ofFrontiers in endocrinology · 2024Article
- Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer.Frontiers in oncology · 2024Review
- Article
- Study of single nucleotide polymorphism of vascular endothelium factor in patients with differentiated thyroid cancer.Clinical diabetes and endocrinology · 2022Article
- Review
- Interpretation of the role of germline and somatic non-coding mutations in cancer: expression and chromatin conformation informed analysis.Clinical epigenetics · 2022Review
- Mendelian Randomization and GWAS Meta Analysis Revealed the Risk-Increasing Effect of Schizophrenia on Cancers.Biology · 2022Article
- Genetic susceptibility to hereditary non-medullary thyroid cancer.Hereditary cancer in clinical practice · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
The [A] allele of SNP rs965513 in 9q22 has been consistently shown to be highly associated with increased papillary thyroid cancer (PTC) risk with an odds ratio of ∼1.8 as determined by genome-wide association studies, yet the molecular mechanisms remain poorly understood. Previously, we noted that the expression of two genes in the region, forkhead box E1 (FOXE1) and PTC susceptibility candidate 2 (PTCSC2), is regulated by rs965513 in unaffected thyroid tissue, but the underlying mechanisms were not elucidated. Here, we fine-mapped the 9q22 region in PTC and controls and detected an ∼33-kb linkage disequilibrium block (containing the lead SNP rs965513) that significantly associates with PTC risk. Chromatin characteristics and regulatory element signatures in this block disclosed at least three regulatory elements functioning as enhancers. These enhancers harbor at least four SNPs (rs7864322, rs12352658, rs7847449, and rs10759944) that serve as functional variants. The variant genotypes are associated with differential enhancer activities and/or transcription factor binding activities. Using the chromosome conformation capture methodology, long-range looping interactions of these elements with the promoter region shared by FOXE1 and PTCSC2 in a human papillary thyroid carcinoma cell line (KTC-1) and unaffected thyroid tissue were found. Our results suggest that multiple variants coinherited with the lead SNP and located in long-range enhancers are involved in the transcriptional regulation of FOXE1 and PTCSC2 expression. These results explain the mechanism by which the risk allele of rs965513 predisposes to thyroid cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.