Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.
Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.
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DOI：
10.1038/s41467-023-42284-5
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发表时间：
2023-10-23
影响因子：
16.6
通讯作者：
John, Catherine
中科院分区：
文献类型：
--
作者：
Williams, Alexander T.;Chen, Jing;Coley, Kayesha;Batini, Chiara;Izquierdo, Abril;Packer, Richard;Abner, Erik;Kanoni, Stavroula;Shepherd, David J.;Free, Robert C.;Hollox, Edward J.;Brunskill, Nigel J.;Ntalla, Ioanna;Reeve, Nicola;Brightling, Christopher E.;Venn, Laura;Adams, Emma;Bee, Catherine;Wallace, Susan E.;Pareek, Manish;Hansell, Anna L.;Esko, Tonu;Stow, Daniel;Jacobs, Benjamin M.;van Heel, David A.;Rao, Balasubramanya S.;Hennah, William;Rao, Balasubramanya S.;Dudbridge, Frank;Wain, Louise V.;Shrine, Nick;Tobin, Martin D.;John, Catherine
甲状腺激素在多种生理功能的调节中起着关键作用，甲状腺功能障碍与大量的发病率有关。在这里，我们使用电子健康记录进行促甲状腺激素（TSH）水平的全基因组关联研究，总样本量为247，107。我们确定了158种新的遗传关联，是已知与TSH关联的数量的两倍多，并涉及112个假定的致病基因，其中76个以前没有涉及。TSH的多基因评分与非洲、南亚、东亚、中东和混合美国血统的TSH水平相关，并与南亚人的甲状腺功能减退症和其他甲状腺疾病相关。在欧洲，TSH多基因评分与甲状腺疾病相关，包括甲状腺癌和甲状腺功能减退症和甲状腺功能亢进症的发病年龄。我们开发了TSH水平的特定途径遗传风险评分，并将其用于全表型关联研究，以确定途径干扰的潜在后果。总之，这些发现表明遗传关联在为甲状腺疾病的未来治疗和风险预测提供信息方面的潜在效用。甲状腺激素在多种生理功能的调节中起着关键作用。在这里，作者通过荟萃分析和详细的变体-基因作图策略，揭示了甲状腺功能和疾病的新基因、途径和关联。
Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases. Thyroid hormones play a critical role in regulation of multiple physiological functions. Here the authors via meta-analyses and detailed variant-to-gene mapping strategies implicate novel genes, pathways and associations for thyroid function and disease.
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影响因子：
64.8
作者：
Kurki, Mitja, I;Karjalainen, Juha;Palta, Priit;Sipila, Timo P.;Kristiansson, Kati;Donner, Kati M.;Reeve, Mary P.;Laivuori, Hannele;Aavikko, Mervi;Kaunisto, Mari A.;Loukola, Anu;Lahtela, Elisa;Mattsson, Hannele;Laiho, Paivi;Parolo, Pietro Della Briotta;Lehisto, Arto A.;Kanai, Masahiro;Mars, Nina;Ramo, Joel;Kiiskinen, Tuomo;Heyne, Henrike O.;Veerapen, Kumar;Rueger, Sina;Lemmela, Susanna;Zhou, Wei;Ruotsalainen, Sanni;Parn, Kalle;Hiekkalinna, Tero;Koskelainen, Sami;Paajanen, Teemu;Llorens, Vincent;Gracia-Tabuenca, Javier;Siirtola, Harri;Reis, Kadri;Elnahas, Abdelrahman G.;Sun, Benjamin;Foley, Christopher N.;Aalto-Setala, Katriina;Alasoo, Kaur;Arvas, Mikko;Auro, Kirsi;Biswas, Shameek;Bizaki-Vallaskangas, Argyro;Carpen, Olli;Chen, Chia-Yen;Dada, Oluwaseun A.;Ding, Zhihao;Ehm, Margaret G.;Eklund, Kari;Farkkila, Martti;Finucane, Hilary;Ganna, Andrea;Ghazal, Awaisa;Graham, Robert R.;Green, Eric M.;Hakanen, Antti;Hautalahti, Marco;Hedman, Asa K.;Hiltunen, Mikko;Hinttala, Reetta;Hovatta, Iiris;Hu, Xinli;Huertas-Vazquez, Adriana;Huilaja, Laura;Hunkapiller, Julie;Jacob, Howard;Jensen, Jan-Nygaard;Joensuu, Heikki;John, Sally;Julkunen, Valtteri;Jung, Marc;Junttila, Juhani;Kaarniranta, Kai;Kahonen, Mika;Kajanne, Risto;Kallio, Lila;Kalviainen, Reetta;Kaprio, Jaakko;Kerimov, Nurlan;Kettunen, Johannes;Kilpelainen, Elina;Kilpi, Terhi;Klinger, Katherine;Kosma, Veli-Matti;Kuopio, Teijo;Kurra, Venla;Laisk, Triin;Laukkanen, Jari;Lawless, Nathan;Liu, Aoxing;Longerich, Simonne;Magi, Reedik;Makela, Johanna;Makitie, Antti;Malarstig, Anders;Mannermaa, Arto;Maranville, Joseph;Matakidou, Athena;Meretoja, Tuomo;Mozaffari, Sahar, V;Niemi, Mari E. K.;Niemi, Marianna;Niiranen, Teemu;Okafo, George;Ollila, Hanna M.;Palomaki, Antti;Palotie, Tuula;Partanen, Jukka;Paul, Dirk S.;Pelkonen, Margit;Pendergrass, Rion K.;Petrovski, Slave;Pitkaranta, Anne;Platt, Adam;Pulford, David;Punkka, Eero;Pussinen, Pirkko;Raghavan, Neha;Rahimov, Fedik;Rajpal, Deepak;Renaud, Nicole A.;Riley-Gillis, Bridget;Rodosthenous, Rodosthenis;Saarentaus, Elmo;Salminen, Aino;Salminen, Eveliina;Salomaa, Veikko;Schleutker, Johanna;Serpi, Raisa;Shen, Huei-yi;Siegel, Richard;Silander, Kaisa;Siltanen, Sanna;Soini, Sirpa;Soininen, Hilkka;Sul, Jae Hoon;Tachmazidou, Ioanna;Tasanen, Kaisa;Tienari, Pentti;Toppila-Salmi, Sanna;Tukiainen, Taru;Tuomi, Tiinamaija;Turunen, Joni A.;Ulirsch, Jacob C.;Vaura, Felix;Virolainen, Petri;Waring, Jeffrey;Waterworth, Dawn;Yang, Robert;Nelis, Mari;Reigo, Anu;Metspalu, Andres;Milani, Lili;Esko, Tonu;Fox, Caroline;Havulinna, Aki S.;Perola, Markus;Ripatti, Samuli;Jalanko, Anu;Laitinen, Tarja;Makela, Tomi P.;Plenge, Robert;McCarthy, Mark;Runz, Heiko;Daly, Mark J.;Palotie, Aarno
通讯作者：
Palotie, Aarno
影响因子：
11
作者：
Fabbri C;Hagenaars SP;John C;Williams AT;Shrine N;Moles L;Hanscombe KB;Serretti A;Shepherd DJ;Free RC;Wain LV;Tobin MD;Lewis CM
通讯作者：
Lewis CM
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL