Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer
Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown. To identify the genetic variants associated with susceptibility to thyroid nodules in com...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2018-12, Vol.103 (12), p.4384-4394 |
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| creator | Hwangbo, Yul Lee, Eun Kyung Son, Ho-Young Im, Sun-Wha Kwak, Soo-Jung Yoon, Ji Won Kim, Min Joo Kim, Jeongseon Choi, Hoon Sung Ryu, Chang Hwan Lee, You Jin Kim, Jong-Il Cho, Nam H Park, Young Joo |
| description | Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown.
To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer.
We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data.
The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues.
To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer. |
| doi_str_mv | 10.1210/jc.2017-02439 |
| format | Article |
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To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer.
We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data.
The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues.
To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2017-02439</identifier><identifier>PMID: 30099483</identifier><language>eng</language><publisher>United States: Copyright Oxford University Press</publisher><subject>Adult ; Biomarkers, Tumor - genetics ; Cohort Studies ; Female ; Gene Frequency ; Genetic diversity ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genotypes ; Health risk assessment ; Humans ; Male ; Middle Aged ; Nodules ; Polymorphism, Single Nucleotide ; Population studies ; Prevalence ; Quantitative trait loci ; Quantitative Trait Loci - genetics ; Republic of Korea - epidemiology ; Risk factors ; Susceptibility ; Thyroid cancer ; Thyroid Gland - diagnostic imaging ; Thyroid Neoplasms - diagnosis ; Thyroid Neoplasms - epidemiology ; Thyroid Neoplasms - genetics ; Thyroid Nodule - diagnosis ; Thyroid Nodule - epidemiology ; Thyroid Nodule - genetics ; Thyroid Nuclear Factor 1 - genetics ; Thyroid transcription factor 1 ; Transient receptor potential proteins ; TRPM Cation Channels - genetics</subject><ispartof>The journal of clinical endocrinology and metabolism, 2018-12, Vol.103 (12), p.4384-4394</ispartof><rights>Copyright © Oxford University Press 2015</rights><rights>Copyright © 2018 Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4479-494ef72ecf7789f8f4b9c4140bb774a9cb931d2cb21314a6c8b6f53aa221228d3</citedby><cites>FETCH-LOGICAL-c4479-494ef72ecf7789f8f4b9c4140bb774a9cb931d2cb21314a6c8b6f53aa221228d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2364254130?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,21388,21389,27924,27925,33530,33531,33744,33745,43659,43805,64385,64387,64389,72469,73123,73128,73129,73131</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30099483$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hwangbo, Yul</creatorcontrib><creatorcontrib>Lee, Eun Kyung</creatorcontrib><creatorcontrib>Son, Ho-Young</creatorcontrib><creatorcontrib>Im, Sun-Wha</creatorcontrib><creatorcontrib>Kwak, Soo-Jung</creatorcontrib><creatorcontrib>Yoon, Ji Won</creatorcontrib><creatorcontrib>Kim, Min Joo</creatorcontrib><creatorcontrib>Kim, Jeongseon</creatorcontrib><creatorcontrib>Choi, Hoon Sung</creatorcontrib><creatorcontrib>Ryu, Chang Hwan</creatorcontrib><creatorcontrib>Lee, You Jin</creatorcontrib><creatorcontrib>Kim, Jong-Il</creatorcontrib><creatorcontrib>Cho, Nam H</creatorcontrib><creatorcontrib>Park, Young Joo</creatorcontrib><title>Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown.
To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer.
We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data.
The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues.
To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.</description><subject>Adult</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotypes</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nodules</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population studies</subject><subject>Prevalence</subject><subject>Quantitative trait loci</subject><subject>Quantitative Trait Loci - genetics</subject><subject>Republic of Korea - epidemiology</subject><subject>Risk factors</subject><subject>Susceptibility</subject><subject>Thyroid cancer</subject><subject>Thyroid Gland - diagnostic imaging</subject><subject>Thyroid Neoplasms - diagnosis</subject><subject>Thyroid Neoplasms - epidemiology</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Nodule - diagnosis</subject><subject>Thyroid Nodule - epidemiology</subject><subject>Thyroid Nodule - genetics</subject><subject>Thyroid Nuclear Factor 1 - genetics</subject><subject>Thyroid transcription factor 1</subject><subject>Transient receptor potential proteins</subject><subject>TRPM Cation Channels - genetics</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kU1v1DAQhi1ERZfCkSuyxKUXt_6YrONjtdCCVIFEi-BmJc5E6yWJF9tptf8eL9v20AO-jDx65tFoXkLeCX4mpODnG3cmudCMS1DmBVkIAxXTwuiXZMG5FMxo-euYvE5pw7kAqNQrcqw4NwZqtSDDFU5hRPbTd0gvUgrON9mHid7kudvR73iHzZDoR5-yn1ymBcfsHb2Zk8Nt9q0ffN7R0NPb9S4G39GvoZsHTPQyhvGpuWomh_ENOeqLDd8-1BPy4_LT7eozu_529WV1cc0cgDYMDGCvJbpe69r0dQ-tcSCAt63W0BjXGiU66VoplIBm6ep22VeqaaQUUtadOiGnB-82hj8zpmxHX9YdhmbCMCcrea2NqapKFfTDM3QT5jiV7axUS5AVCMULxQ6UiyGliL3dRj82cWcFt_sY7MbZfQz2XwyFf_9gndsRuyf68e4FEAfgPgwZY_o9zPcY7bocO6-fS9mjFP4zw8uDpa5ZmaiFLD-2b2n1F2N9oho</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Hwangbo, Yul</creator><creator>Lee, Eun Kyung</creator><creator>Son, Ho-Young</creator><creator>Im, Sun-Wha</creator><creator>Kwak, Soo-Jung</creator><creator>Yoon, Ji Won</creator><creator>Kim, Min Joo</creator><creator>Kim, Jeongseon</creator><creator>Choi, Hoon Sung</creator><creator>Ryu, Chang Hwan</creator><creator>Lee, You Jin</creator><creator>Kim, Jong-Il</creator><creator>Cho, Nam H</creator><creator>Park, Young Joo</creator><general>Copyright Oxford University Press</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201812</creationdate><title>Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer</title><author>Hwangbo, Yul ; Lee, Eun Kyung ; Son, Ho-Young ; Im, Sun-Wha ; Kwak, Soo-Jung ; Yoon, Ji Won ; Kim, Min Joo ; Kim, Jeongseon ; Choi, Hoon Sung ; Ryu, Chang Hwan ; Lee, You Jin ; Kim, Jong-Il ; Cho, Nam H ; Park, Young Joo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4479-494ef72ecf7789f8f4b9c4140bb774a9cb931d2cb21314a6c8b6f53aa221228d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotypes</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nodules</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population studies</topic><topic>Prevalence</topic><topic>Quantitative trait loci</topic><topic>Quantitative Trait Loci - genetics</topic><topic>Republic of Korea - epidemiology</topic><topic>Risk factors</topic><topic>Susceptibility</topic><topic>Thyroid cancer</topic><topic>Thyroid Gland - diagnostic imaging</topic><topic>Thyroid Neoplasms - diagnosis</topic><topic>Thyroid Neoplasms - epidemiology</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Nodule - diagnosis</topic><topic>Thyroid Nodule - epidemiology</topic><topic>Thyroid Nodule - genetics</topic><topic>Thyroid Nuclear Factor 1 - genetics</topic><topic>Thyroid transcription factor 1</topic><topic>Transient receptor potential proteins</topic><topic>TRPM Cation Channels - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hwangbo, Yul</creatorcontrib><creatorcontrib>Lee, Eun Kyung</creatorcontrib><creatorcontrib>Son, Ho-Young</creatorcontrib><creatorcontrib>Im, Sun-Wha</creatorcontrib><creatorcontrib>Kwak, Soo-Jung</creatorcontrib><creatorcontrib>Yoon, Ji Won</creatorcontrib><creatorcontrib>Kim, Min Joo</creatorcontrib><creatorcontrib>Kim, Jeongseon</creatorcontrib><creatorcontrib>Choi, Hoon Sung</creatorcontrib><creatorcontrib>Ryu, Chang Hwan</creatorcontrib><creatorcontrib>Lee, You Jin</creatorcontrib><creatorcontrib>Kim, Jong-Il</creatorcontrib><creatorcontrib>Cho, Nam H</creatorcontrib><creatorcontrib>Park, Young Joo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hwangbo, Yul</au><au>Lee, Eun Kyung</au><au>Son, Ho-Young</au><au>Im, Sun-Wha</au><au>Kwak, Soo-Jung</au><au>Yoon, Ji Won</au><au>Kim, Min Joo</au><au>Kim, Jeongseon</au><au>Choi, Hoon Sung</au><au>Ryu, Chang Hwan</au><au>Lee, You Jin</au><au>Kim, Jong-Il</au><au>Cho, Nam H</au><au>Park, Young Joo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2018-12</date><risdate>2018</risdate><volume>103</volume><issue>12</issue><spage>4384</spage><epage>4394</epage><pages>4384-4394</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown.
To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer.
We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data.
The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues.
To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.</abstract><cop>United States</cop><pub>Copyright Oxford University Press</pub><pmid>30099483</pmid><doi>10.1210/jc.2017-02439</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Biomarkers, Tumor - genetics Cohort Studies Female Gene Frequency Genetic diversity Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genotypes Health risk assessment Humans Male Middle Aged Nodules Polymorphism, Single Nucleotide Population studies Prevalence Quantitative trait loci Quantitative Trait Loci - genetics Republic of Korea - epidemiology Risk factors Susceptibility Thyroid cancer Thyroid Gland - diagnostic imaging Thyroid Neoplasms - diagnosis Thyroid Neoplasms - epidemiology Thyroid Neoplasms - genetics Thyroid Nodule - diagnosis Thyroid Nodule - epidemiology Thyroid Nodule - genetics Thyroid Nuclear Factor 1 - genetics Thyroid transcription factor 1 Transient receptor potential proteins TRPM Cation Channels - genetics |
| title | Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules From Thyroid Cancer |
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