{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:24Z","timestamp":1784557164739,"version":"3.55.0"},"reference-count":45,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["etj.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,28]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic\u2013pituitary\u2013thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the\n                      <jats:italic>CAPZB<\/jats:italic>\n                      locus that were differentially associated with\n                      <jats:italic>CAPZB<\/jats:italic>\n                      expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these,\n                      <jats:italic>ANXA5<\/jats:italic>\n                      expression and plasma annexin A5 levels were inversely associated with TSH (PWAS:\n                      <jats:italic>P<\/jats:italic>\n                      = 1.18 \u00d7 10\n                      <jats:sup>\u221213<\/jats:sup>\n                      , TWAS:\n                      <jats:italic>P<\/jats:italic>\n                      = 7.61 \u00d7 10\n                      <jats:sup>\u221212<\/jats:sup>\n                      (whole blood),\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20096.40 \u00d7 10\n                      <jats:sup>\u221213<\/jats:sup>\n                      (hypothalamus),\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20091.57 \u00d7 10\n                      <jats:sup>\u221215<\/jats:sup>\n                      (pituitary),\n                      <jats:italic>P<\/jats:italic>\n                      = 4.27 \u00d7 10\n                      <jats:sup>\u221215<\/jats:sup>\n                      (thyroid)), supported by colocalizations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-24-0067","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T13:30:59Z","timestamp":1716903059000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-16","source":"Crossref","is-referenced-by-count":5,"title":["New insights into the hypothalamic\u2013pituitary\u2013thyroid axis: a transcriptome- and proteome-wide association study"],"prefix":"10.1530","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3341-5638","authenticated-orcid":true,"given":"Sara","family":"Monteiro-Martins","sequence":"first","affiliation":[{"name":"Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center \u2013 University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie B T M","family":"Sterenborg","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Borisov","sequence":"additional","affiliation":[{"name":"Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center \u2013 University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Scherer","sequence":"additional","affiliation":[{"name":"Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center \u2013 University of Freiburg, Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center \u2013 University of Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-7858","authenticated-orcid":true,"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"K\u00f6ttgen","sequence":"additional","affiliation":[{"name":"Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center \u2013 University of Freiburg, Freiburg, Germany"},{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-094X","authenticated-orcid":true,"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endotext","article-title":"Ontogeny, anatomy, metabolism and physiology of the thyroid","author":"Maenhaut","year":"2015","unstructured":"Maenhaut CChristophe DVassart GDumont JRoger PP & Opitz R. Ontogeny, anatomy, metabolism and physiology of the thyroid . InEndotext. KR Feingold, B Anawalt, MR Blackman (editors)South Dartmouth, MA: MDText.com, Inc.2015. Available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK285554\/."},{"key":"bib2","series-title":"Endocrine Reviews","first-page":"214","article-title":"Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand?","volume":"36","author":"Medici","year":"2015","unstructured":"Medici MVisser WEVisser TJ & Peeters RP. Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand?Endocrine Reviews201536214\u2013244. (https:\/\/doi.org\/10.1210\/er.2014-1081)"},{"key":"bib3","series-title":"Endocrinology and Metabolism Clinics of North America","first-page":"375","article-title":"Defects of thyroid hormone synthesis and action","volume":"46","author":"Hannoush","year":"2017","unstructured":"Hannoush ZC & Weiss RE. Defects of thyroid hormone synthesis and action. Endocrinology and Metabolism Clinics of North America201746375\u2013388. (https:\/\/doi.org\/10.1016\/j.ecl.2017.01.005)"},{"key":"bib4","series-title":"Nature Communications","first-page":"4455","article-title":"Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation","volume":"9","author":"Teumer","year":"2018","unstructured":"Teumer AChaker LGroeneweg SLi YDi Munno CBarbieri CSchultheiss UTTraglia MAhluwalia TSAkiyama M, et al.Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nature Communications201894455. (https:\/\/doi.org\/10.1038\/s41467-018-06356-1)"},{"key":"bib5","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"e2276","article-title":"The effects of common genetic variation in 96 genes involved in thyroid hormone regulation on TSH and FT4 concentrations","volume":"107","author":"Sterenborg","year":"2022","unstructured":"Sterenborg RBTMGalesloot TETeumer ANetea-Maier RTSpeed DMeima MEVisser WESmit JWAPeeters RP & Medici M. The effects of common genetic variation in 96 genes involved in thyroid hormone regulation on TSH and FT4 concentrations. Journal of Clinical Endocrinology and Metabolism2022107e2276\u2013e2283. (https:\/\/doi.org\/10.1210\/clinem\/dgac136)"},{"key":"bib6","series-title":"Nature Communications","first-page":"888","article-title":"Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications","volume":"15","author":"Sterenborg","year":"2024","unstructured":"Sterenborg RBTMSteinbrenner ILi YBujnis MNNaito TMarouli EGalesloot TEBabajide OAndreasen LAstrup A, et al.Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications. Nature Communications202415888. (https:\/\/doi.org\/10.1038\/s41467-024-44701-9)"},{"key":"bib7","series-title":"Nature Genetics","first-page":"592","article-title":"Opportunities and challenges for transcriptome-wide association studies","volume":"51","author":"Wainberg","year":"2019","unstructured":"Wainberg MSinnott-Armstrong NMancuso NBarbeira ANKnowles DAGolan DErmel RRuusalepp AQuertermous THao K, et al.Opportunities and challenges for transcriptome-wide association studies. Nature Genetics201951592\u2013599. (https:\/\/doi.org\/10.1038\/s41588-019-0385-z)"},{"key":"bib8","series-title":"Frontiers in Genetics","first-page":"713230","article-title":"From GWAS to gene: transcriptome-wide association studies and other methods to functionally understand GWAS discoveries","volume":"12","author":"Li","year":"2021","unstructured":"Li B & Ritchie MD. From GWAS to gene: transcriptome-wide association studies and other methods to functionally understand GWAS discoveries. Frontiers in Genetics202112713230. (https:\/\/doi.org\/10.3389\/fgene.2021.713230)"},{"key":"bib9","series-title":"Science","first-page":"1318","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","year":"2020","unstructured":"GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science20203691318\u20131330. (https:\/\/doi.org\/10.1126\/science.aaz1776)"},{"key":"bib10","series-title":"Biopreservation and Biobanking","first-page":"311","article-title":"A novel approach to high-quality postmortem tissue procurement: the GTEx project","volume":"13","author":"Carithers","year":"2015","unstructured":"Carithers LJArdlie KBarcus MBranton PABritton ABuia SACompton CCDeLuca DSPeter-Demchok JGelfand ET, et al.A novel approach to high-quality postmortem tissue procurement: the GTEx project. Biopreservation and Biobanking201513311\u2013319. (https:\/\/doi.org\/10.1089\/bio.2015.0032)"},{"key":"bib11","series-title":"Nature Genetics","first-page":"593","article-title":"Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies","volume":"54","author":"Zhang","year":"2022","unstructured":"Zhang JDutta DK\u00f6ttgen ATin ASchlosser PGrams MEHarvey BYu BBoerwinkle ECoresh J, et al.Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies. Nature Genetics202254593\u2013602. (https:\/\/doi.org\/10.1038\/s41588-022-01051-w)"},{"key":"bib12","series-title":"Bioinformatics","first-page":"1841","article-title":"rtracklayer: an R package for interfacing with genome browsers","volume":"25","author":"Lawrence","year":"2009","unstructured":"Lawrence MGentleman R & Carey V. rtracklayer: an R package for interfacing with genome browsers. Bioinformatics2009251841\u20131842. (https:\/\/doi.org\/10.1093\/bioinformatics\/btp328)"},{"key":"bib13","series-title":"Nature Genetics","first-page":"245","article-title":"Integrative approaches for large-scale transcriptome-wide association studies","volume":"48","author":"Gusev","year":"2016","unstructured":"Gusev AKo AShi HBhatia GChung WPenninx BWJHJansen Rde Geus EJCBoomsma DIWright FA, et al.Integrative approaches for large-scale transcriptome-wide association studies. Nature Genetics201648245\u2013252. (https:\/\/doi.org\/10.1038\/ng.3506)"},{"key":"bib14","series-title":"American Journal of Human Genetics","first-page":"76","article-title":"GCTA: a tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","unstructured":"Yang JLee SHGoddard ME & Visscher PM. GCTA: a tool for genome-wide complex trait analysis. American Journal of Human Genetics20118876\u201382. (https:\/\/doi.org\/10.1016\/j.ajhg.2010.11.011)"},{"key":"bib15","series-title":"Genetic Epidemiology","first-page":"79","article-title":"Bayes factors for genome-wide association studies: comparison with P-values","volume":"33","author":"Wakefield","year":"2009","unstructured":"Wakefield J. Bayes factors for genome-wide association studies: comparison with P-values. Genetic Epidemiology20093379\u201386. (https:\/\/doi.org\/10.1002\/gepi.20359)"},{"key":"bib16","series-title":"PLoS Genetics","first-page":"e1004383","article-title":"Bayesian test for colocalisation between pairs of genetic association studies using summary statistics","volume":"10","author":"Giambartolomei","year":"2014","unstructured":"Giambartolomei CVukcevic DSchadt EEFranke LHingorani ADWallace C & Plagnol V. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genetics201410e1004383. (https:\/\/doi.org\/10.1371\/journal.pgen.1004383)"},{"key":"bib17","series-title":"Nature Genetics","first-page":"25","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","unstructured":"Ashburner MBall CABlake JABotstein DButler HCherry JMDavis APDolinski KDwight SSEppig JT, et al.Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature Genetics20002525\u201329. (https:\/\/doi.org\/10.1038\/75556)"},{"key":"bib18","series-title":"Nucleic Acids Research","first-page":"27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","unstructured":"Kanehisa M & Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Research20002827\u201330. (https:\/\/doi.org\/10.1093\/nar\/28.1.27)"},{"key":"bib19","series-title":"Science","first-page":"1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","unstructured":"Uhl\u00e9n MFagerberg LHallstr\u00f6m BMLindskog COksvold PMardinoglu ASivertsson \u00c5Kampf CSj\u00f6stedt EAsplund A, et al.Proteomics. Tissue-based map of the human proteome. Science20153471260419. (https:\/\/doi.org\/10.1126\/science.1260419)"},{"key":"bib20","series-title":"Nature Genetics","first-page":"995","article-title":"Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine","volume":"55","author":"Schlosser","year":"2023","unstructured":"Schlosser PScherer NGrundner-Culemann FMonteiro-Martins SHaug SSteinbrenner IUluvar BWuttke MCheng YEkici AB, et al.Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine. Nature Genetics202355995\u20131008. (https:\/\/doi.org\/10.1038\/s41588-023-01409-8)"},{"key":"bib21","series-title":"Innovation","first-page":"100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","unstructured":"Wu THu EXu SChen MGuo PDai ZFeng TZhou LTang WZhan L, et al.clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation20212100141. (https:\/\/doi.org\/10.1016\/j.xinn.2021.100141)"},{"key":"bib22","series-title":"Journal of the Royal Statistical Society Series B","first-page":"289","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","unstructured":"Benjamini Y & Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B199557289\u2013300. (https:\/\/doi.org\/10.1111\/j.2517-6161.1995.tb02031.x)"},{"key":"bib23","series-title":"Nature","first-page":"527","article-title":"Rare variant contribution to human disease in 281,104 UK Biobank exomes","volume":"597","author":"Wang","year":"2021","unstructured":"Wang QDhindsa RSCarss KHarper ARNag ATachmazidou IVitsios DDeevi SVVMackay AMuthas D, et al.Rare variant contribution to human disease in 281,104 UK Biobank exomes. Nature2021597527\u2013532. (https:\/\/doi.org\/10.1038\/s41586-021-03855-y)"},{"key":"bib24","series-title":"Nature Genetics","first-page":"550","article-title":"Exploring and visualizing large-scale genetic associations using PheWeb","volume":"52","author":"Gagliano Taliun","year":"2020","unstructured":"Gagliano Taliun SAVandeHaar PBoughton APWelch RPTaliun DSchmidt EMZhou WNielsen JBWiller CJLee S, et al.Exploring and visualizing large-scale genetic associations using PheWeb. Nature Genetics202052550\u2013552. (https:\/\/doi.org\/10.1038\/s41588-020-0622-5)"},{"key":"bib25","series-title":"Physiological Reviews","first-page":"331","article-title":"Annexins: from structure to function","volume":"82","author":"Gerke","year":"2002","unstructured":"Gerke V & Moss SE. Annexins: from structure to function. Physiological Reviews200282331\u2013371. (https:\/\/doi.org\/10.1152\/physrev.00030.2001)"},{"key":"bib26","series-title":"International Journal of Cardiology","first-page":"131","article-title":"Effect of calcium channel blockers on serum levels of thyroid hormones","volume":"38","author":"Mittal","year":"1993","unstructured":"Mittal SRMathur AK & Prasad N. Effect of calcium channel blockers on serum levels of thyroid hormones. International Journal of Cardiology199338131\u2013132. (https:\/\/doi.org\/10.1016\/0167-5273(9390171-c)"},{"key":"bib27","series-title":"Journal of Physiology","first-page":"19","article-title":"The role of peptide YY in appetite regulation and obesity","volume":"587","author":"Karra","year":"2009","unstructured":"Karra EChandarana K & Batterham RL. The role of peptide YY in appetite regulation and obesity. Journal of Physiology200958719\u201325. (https:\/\/doi.org\/10.1113\/jphysiol.2008.164269)"},{"key":"bib28","series-title":"Endocrine Reviews","first-page":"347","article-title":"PCSK1 mutations and human endocrinopathies: from obesity to gastrointestinal disorders","volume":"37","author":"Stijnen","year":"2016","unstructured":"Stijnen PRamos-Molina BO\u2019Rahilly S & Creemers JWM. PCSK1 mutations and human endocrinopathies: from obesity to gastrointestinal disorders. Endocrine Reviews201637347\u2013371. (https:\/\/doi.org\/10.1210\/er.2015-1117)"},{"key":"bib29","series-title":"Journal of Molecular Endocrinology","first-page":"19","article-title":"Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha","volume":"43","author":"Selva","year":"2009","unstructured":"Selva DM & Hammond GL. Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha. Journal of Molecular Endocrinology20094319\u201327. (https:\/\/doi.org\/10.1677\/JME-09-0025)"},{"key":"bib30","series-title":"Human Molecular Genetics","first-page":"1871","article-title":"Transcriptome-wide association study identifies multiple genes and pathways associated with thyroid function","volume":"31","author":"Ke","year":"2022","unstructured":"Ke XTian XYao SWu HDuan YYWang NNShi WYang TLDong SSHuang D, et al.Transcriptome-wide association study identifies multiple genes and pathways associated with thyroid function. Human Molecular Genetics2022311871\u20131883. (https:\/\/doi.org\/10.1093\/hmg\/ddab371)"},{"key":"bib31","series-title":"Molecular and Cellular Endocrinology","first-page":"111173","article-title":"The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions","volume":"525","author":"Feldt-Rasmussen","year":"2021","unstructured":"Feldt-Rasmussen UEffraimidis G & Klose M. The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions. Molecular and Cellular Endocrinology2021525111173. (https:\/\/doi.org\/10.1016\/j.mce.2021.111173)"},{"key":"bib32","series-title":"Endocrine Reviews","first-page":"159","article-title":"Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions","volume":"35","author":"Fekete","year":"2014","unstructured":"Fekete C & Lechan RM. Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocrine Reviews201435159\u2013194. (https:\/\/doi.org\/10.1210\/er.2013-1087)"},{"key":"bib33","series-title":"Molecular and Cellular Endocrinology","first-page":"1","article-title":"Pituitary cell lines and their endocrine applications","volume":"228","author":"Ooi","year":"2004","unstructured":"Ooi GTTawadros N & Escalona RM. Pituitary cell lines and their endocrine applications. Molecular and Cellular Endocrinology20042281\u201321. (https:\/\/doi.org\/10.1016\/j.mce.2004.07.018)"},{"key":"bib34","series-title":"International Journal of Molecular Sciences","first-page":"3393","article-title":"Selenium, iodine and iron-essential trace elements for thyroid hormone synthesis and metabolism","volume":"24","author":"K\u00f6hrle","year":"2023","unstructured":"K\u00f6hrle J. Selenium, iodine and iron-essential trace elements for thyroid hormone synthesis and metabolism. International Journal of Molecular Sciences2023243393. (https:\/\/doi.org\/10.3390\/ijms24043393)"},{"key":"bib35","series-title":"Nature Reviews. Disease Primers","first-page":"30","article-title":"Hypothyroidism","volume":"8","author":"Chaker","year":"2022","unstructured":"Chaker LRazvi SBensenor IMAzizi FPearce EN & Peeters RP. Hypothyroidism. Nature Reviews. Disease Primers2022830. (https:\/\/doi.org\/10.1038\/s41572-022-00357-7)"},{"key":"bib36","series-title":"American Journal of Human Genetics","first-page":"664","article-title":"Genome-wide association study identifies four genetic loci associated with thyroid volume and goiter risk","volume":"88","author":"Teumer","year":"2011","unstructured":"Teumer ARawal RHomuth GErnst FHeier MEvert MDombrowski FV\u00f6lker UNauck MRadke D, et al.Genome-wide association study identifies four genetic loci associated with thyroid volume and goiter risk. American Journal of Human Genetics201188664\u2013673. (https:\/\/doi.org\/10.1016\/j.ajhg.2011.04.015)"},{"key":"bib37","series-title":"European Journal of Biochemistry","first-page":"506","article-title":"In vivo modulation of annexins I, II and V expression by thyroxine and methylthiouracil","volume":"242","author":"el Btaouri","year":"1996","unstructured":"el Btaouri HClaisse DBellon GAntonicelli F & Haye B. In vivo modulation of annexins I, II and V expression by thyroxine and methylthiouracil. European Journal of Biochemistry1996242506\u2013511. (https:\/\/doi.org\/10.1111\/j.1432-1033.1996.0506r.x)"},{"key":"bib38","series-title":"Biochimie","first-page":"417","article-title":"Cyclic AMP regulation of annexins I, II, V synthesis and localization in cultured porcine thyroid cells","volume":"76","author":"Elbtaouri","year":"1994","unstructured":"Elbtaouri HAntonicelli FClaisse DDelemer B & Haye B. Cyclic AMP regulation of annexins I, II, V synthesis and localization in cultured porcine thyroid cells. Biochimie199476417\u2013422. (https:\/\/doi.org\/10.1016\/0300-9084(9490118-x)"},{"key":"bib39","series-title":"Biochimica et Biophysica Acta","first-page":"352","article-title":"Calcium signaling of thyrocytes is modulated by TSH through calcium binding protein expression","volume":"1803","author":"Lorenz","year":"2010","unstructured":"Lorenz SEszlinger MPaschke RAust GWeick MF\u00fchrer D & Krohn K. Calcium signaling of thyrocytes is modulated by TSH through calcium binding protein expression. Biochimica et Biophysica Acta20101803352\u2013360. (https:\/\/doi.org\/10.1016\/j.bbamcr.2010.01.007)"},{"key":"bib40","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"2601","article-title":"Melanocortin 4 receptor pathway dysfunction in obesity: patient stratification aimed at MC4R agonist treatment","volume":"103","author":"Ayers","year":"2018","unstructured":"Ayers KLGlicksberg BSGarfield ASLongerich SWhite JAYang PDu LChittenden TWGulcher JRRoy S, et al.Melanocortin 4 receptor pathway dysfunction in obesity: patient stratification aimed at MC4R agonist treatment. Journal of Clinical Endocrinology and Metabolism20181032601\u20132612. (https:\/\/doi.org\/10.1210\/jc.2018-00258)"},{"key":"bib41","series-title":"PLoS One","first-page":"e108878","article-title":"A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1\/3 and impairs its enzymatic activity","volume":"9","author":"Wilschanski","year":"2014","unstructured":"Wilschanski MAbbasi MBlanco ELindberg IYourshaw MZangen DBerger IShteyer EPappo OBar-Oz B, et al.A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1\/3 and impairs its enzymatic activity. PLoS One20149e108878. (https:\/\/doi.org\/10.1371\/journal.pone.0108878)"},{"key":"bib42","series-title":"Journal of Human Genetics","first-page":"625","article-title":"Variation in the SERPINA6\/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease","volume":"66","author":"Crawford","year":"2021","unstructured":"Crawford AABankier SAltmaier EBarnes CLKClark DWErmel RFriedrich Nvan der Harst PJoshi PKKarhunen V, et al.Variation in the SERPINA6\/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease. Journal of Human Genetics202166625\u2013636. (https:\/\/doi.org\/10.1038\/s10038-020-00895-6)"},{"key":"bib43","article-title":"Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes - PubMed","unstructured":"Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes - PubMed [Internet]. [cited 2024 Jan 28]. Available at: https:\/\/pubmed.ncbi.nlm.nih.gov\/26014426\/."},{"key":"bib44","series-title":"Bioinformatics","first-page":"2336","article-title":"LocusZoom: regional visualization of genome-wide association scan results","volume":"26","author":"Pruim","year":"2010","unstructured":"Pruim RJWelch RPSanna STeslovich TMChines PSGliedt TPBoehnke MAbecasis GR & Willer CJ. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics2010262336\u20132337. (https:\/\/doi.org\/10.1093\/bioinformatics\/btq419)"},{"key":"bib45","series-title":"Nature","first-page":"57","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","year":"2012","unstructured":"ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature201248957\u201374. 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