Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

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Sliz, E. (author)

Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata

Article/chapterEnglish2023

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2023-02-01
Springer Science and Business Media LLC,2023

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LIBRIS-ID:oai:gup.ub.gu.se/329974
https://gup.ub.gu.se/publication/329974URI
https://doi.org/10.1038/s41467-023-35974-7DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:153370600URI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng

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Tyrmi, J. S. (author)
Rahmioglu, N. (author)
Zondervan, K. T. (author)
Becker, C. M. (author)
Uimari, O. (author)
Kettunen, J. (author)
Palotie, A. (author)
Daly, M. (author)
Riley-Gills, B. (author)
Jacob, H. (author)
Paul, D. (author)
Matakidou, A. (author)
Platt, A. (author)
Runz, H. (author)
John, S. (author)
Okafo, G. (author)
Lawless, N. (author)
Salminen-Mankonen, H. (author)
Plenge, R. (author)
Maranville, J. (author)
McCarthy, M. (author)
Ehm, M. G. (author)
Auro, K. (author)
Longerich, S. (author)
Fox, C. (author)
Malarstig, A. (author)
Klinger, K. (author)
Chatelain, C. (author)
Gossel, M. (author)
Estrada, K. (author)
Graham, R. (author)
Yang, R. (author)
O'Donnell, C. (author)
Makela, T. P. (author)
Kaprio, J. (author)
Virolainen, P. (author)
Hakanen, A. (author)
Kilpi, T. (author)
Perola, M. (author)
Partanen, J. (author)
Pitkaranta, A. (author)
Raivio, T. (author)
Serpi, R. (author)
Laitinen, T. (author)
Kosma, V. M. (author)
Laukkanen, J. (author)
Hautalahti, M. (author)
Tuovila, O. (author)
Pakkanen, R. (author)
Waring, J. (author)
Riley-Gillis, B. (author)
Rahimov, F. (author)
Tachmazidou, I. (author)
Chen, C. Y. (author)
Ding, Z. H. (author)
Jung, M. (author)
Biswas, S. (author)
Pendergrass, R. (author)
Pulford, D. (author)
Raghavan, N. (author)
Huertas-Vazquez, A. (author)
Sul, J. H. (author)
Hu, X. L. (author)
Hedman, A. (author)
Rivas, M. (author)
Waterworth, D. (author)
Renaud, N. (author)
Obeidat, M. (author)
Ripatti, S. (author)
Schleutker, J. (author)
Arvas, M.Karolinska Institutet (author)
Carpen, O. (author)
Hinttala, R. (author)
Mannermaa, A. (author)
Aalto-Setala, K. (author)
Kahonen, M. (author)
Makela, J. (author)
Kalviainen, R. (author)
Julkunen, V. (author)
Soininen, H. (author)
Remes, A. (author)
Hiltunen, M. (author)
Peltola, J. (author)
Raivio, M. (author)
Tienari, P. (author)
Rinne, J. (author)
Kallionpaa, R. (author)
Partanen, J. (author)
Abbasi, A. (author)
Ziemann, A. (author)
Smaoui, N. (author)
Lehtonen, A. (author)
Eaton, S. (author)
Lahdenpera, S. (author)
Bowers, N. (author)
Teng, E. (author)
Xu, F. L. (author)
Addis, L. (author)
Eicher, J. (author)
Li, Q. Q. S. (author)
He, K. (author)
Khramtsova, E. (author)
Farkkila, M. (author)
Koskela, J. (author)
Pikkarainen, S. (author)
Jussila, A. (author)
Kaukinen, K. (author)
Blomster, T. (author)
Kiviniemi, M. (author)
Voutilainen, M. (author)
Lu, T. (author)
McCarthy, L. (author)
Hart, A. (author)
Guan, M. J. (author)
Miller, J. (author)
Kalpala, K. (author)
Miller, M. (author)
Eklund, K. (author)
Palomaki, A. (author)
Isomaki, P. (author)
Pirila, L. (author)
Kaipiainen-Seppanen, O. (author)
Huhtakangas, J. (author)
Mars, N. (author)
Lertratanakul, A. (author)
Hochfeld, M. (author)
Gordillo, J. E. (author)
Farias, F. (author)
Bing, N. (author)
Pelkonen, M. (author)
Kauppi, P. (author)
Kankaanranta, Hannu,1967Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xkankh (author)
Harju, T. (author)
Lahesmaa, R. (author)
Lassi, G. (author)
Chen, H. (author)
Betts, J. (author)
Mishra, R. (author)
Mouded, M. (author)
Ngo, D. (author)
Niiranen, T. (author)
Vaura, F. (author)
Salomaa, V. (author)
Metsarinne, K. (author)
Aittokallio, J. (author)
Hernesniemi, J. (author)
Gordin, D. (author)
Sinisalo, J. (author)
Taskinen, M. R. (author)
Tuomi, T. (author)
Hiltunen, T. (author)
Elliott, A. (author)
Reeve, M. P. (author)
Ruotsalainen, S. (author)
Challis, B. (author)
Chu, A. (author)
Reilly, D. (author)
Mendelson, M. (author)
Parkkinen, J. (author)
Meretoja, T. (author)
Joensuu, H. (author)
Mattson, J. (author)
Salminen, E. (author)
Auranen, A. (author)
Karihtala, P. (author)
Auvinen, P. (author)
Elenius, K. (author)
Pitkanen, E. (author)
Popovic, R. (author)
Schutzman, J. (author)
Kulkarni, D. (author)
Porello, A. (author)
Loboda, A. (author)
Lehtonen, H. (author)
McDonough, S. (author)
Vuoti, S. (author)
Kaarniranta, K. (author)
Turunen, J. A. (author)
Ollila, T. (author)
Uusitalo, H. (author)
Karjalainen, J. (author)
Liu, M. Z. (author)
Loomis, S. (author)
Strauss, E. (author)
Chen, H. (author)
Tasanen, K. (author)
Huilaja, L. (author)
Hannula-Jouppi, K. (author)
Salmi, T. (author)
Peltonen, S. (author)
Koulu, L. (author)
Choy, D. (author)
Wu, Y. (author)
Pussinen, P. (author)
Salminen, A. (author)
Salo, T. (author)
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Nieminen, P. (author)
Palotie, U. (author)
Siponen, M. (author)
Suominen, L. (author)
Mantyla, P. (author)
Gursoy, U. (author)
Anttonen, V. (author)
Sipila, K. (author)
Laivuori, H. (author)
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Heikinheimo, O. (author)
Kalliala, I. (author)
Aaltonen, L. (author)
Jokimaa, V. (author)
Vaarasmaki, M. (author)
Morin-Papunen, L. (author)
Niinimaki, M. (author)
Piltonen, T. (author)
Kivinen, K. (author)
Widen, E. (author)
Tukiainen, T. (author)
Valimaki, N. (author)
Laakkonen, E. (author)
Silven, H. (author)
Arffman, R. (author)
Savukoski, S. (author)
Laisk, T. (author)
Pujol, N. (author)
Kumar, J. (author)
Hovatta, I. (author)
Isometsa, E. (author)
Ollila, H. (author)
Suvisaari, J. (author)
Als, T. D. (author)
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Bizaki-Vallaskangas, A. (author)
Toppila-Salmi, S. (author)
Willberg, T. (author)
Saarentaus, E. (author)
Aarnisalo, A. (author)
Rahikkala, E. (author)
Aittomaki, K. (author)
Aberg, F. (author)
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Havulinna, A. (author)
Mehtonen, J. (author)
Palta, P. (author)
Hassan, S. (author)
Parolo, P. D. (author)
Zhou, W. (author)
Maasha, M. (author)
Lemmela, S. (author)
Liu, A. X. (author)
Lehisto, A. (author)
Ganna, A. (author)
Llorens, V. (author)
Heyne, H. (author)
Ramo, J. (author)
Rodosthenous, R. (author)
Strausz, S. (author)
Palotie, T. (author)
Palin, K. (author)
Garcia-Tabuenca, J. (author)
Siirtola, H. (author)
Kiiskinen, T. (author)
Lee, J. (author)
Tsuo, K. (author)
Kristiansson, K. (author)
Hyvarinen, K. (author)
Ritari, J. (author)
Pylkas, K. (author)
Karjalainen, M. (author)
Mantere, T. (author)
Kangasniemi, E. (author)
Heikkinen, S. (author)
Pitkanen, N. (author)
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Punkka, E. (author)
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Jalanko, A. (author)
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Kajanne, R. (author)
Aavikko, M. (author)
Palin, H. (author)
Linna, M. M. (author)
Kanai, M. (author)
Zheng, Z. L. (author)
Lahtela, L. E. (author)
Kaunisto, M. (author)
Kilpelainen, E. (author)
Sipila, T. P. (author)
Dada, O. A. (author)
Ghazal, A. (author)
Kytola, A. (author)
Weldatsadik, R. (author)
Donner, K. (author)
Loukola, A. (author)
Laiho, P. (author)
Sistonen, T. (author)
Kaiharju, E. (author)
Laukkanen, M. (author)
Jarvensivu, E. (author)
Lahteenmaki, S. (author)
Mannikko, L. (author)
Wong, R. (author)
Toivola, A. (author)
Brunfeldt, M. (author)
Mattsson, H. (author)
Koskelainen, S. (author)
Hiekkalinna, T. (author)
Paajanen, T. (author)
Parn, K. (author)
Kals, M. (author)
Luo, S. (author)
Padmanabhuni, S. S. (author)
Niemi, M. (author)
Gracia-Tabuenca, J. (author)
Helminen, M. (author)
Luukkaala, T. (author)
Vahatalo, I. (author)
Tammerluoto, J. (author)
Smith, S. (author)
Southerington, T. (author)
Lehto, P. (author)
Karolinska InstitutetInstitutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition (creator_code:org_t)

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In:Nature Communications: Springer Science and Business Media LLC14:12041-1723

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By the author/editor: Sliz, E.; Tyrmi, J. S.; Rahmioglu, N.; Zondervan, K. T.; Becker, C. M.; Uimari, O.; show more...; Kettunen, J.; Palotie, A.; Daly, M.; Riley-Gills, B.; Jacob, H.; Paul, D.; Matakidou, A.; Platt, A.; Runz, H.; John, S.; Okafo, G.; Lawless, N.; Salminen-Mankone ...; Plenge, R.; Maranville, J.; McCarthy, M.; Ehm, M. G.; Auro, K.; Longerich, S.; Fox, C.; Malarstig, A.; Klinger, K.; Chatelain, C.; Gossel, M.; Estrada, K.; Graham, R.; Yang, R.; O'Donnell, C.; Makela, T. P.; Kaprio, J.; Virolainen, P.; Hakanen, A.; Kilpi, T.; Perola, M.; Partanen, J.; Pitkaranta, A.; Raivio, T.; Serpi, R.; Laitinen, T.; Kosma, V. M.; Laukkanen, J.; Hautalahti, M.; Tuovila, O.; Pakkanen, R.; Waring, J.; Riley-Gillis, B.; Rahimov, F.; Tachmazidou, I.; Chen, C. Y.; Ding, Z. H.; Jung, M.; Biswas, S.; Pendergrass, R.; Pulford, D.; Raghavan, N.; Huertas-Vazquez, ...; Sul, J. H.; Hu, X. L.; Hedman, A.; Rivas, M.; Waterworth, D.; Renaud, N.; Obeidat, M.; Ripatti, S.; Schleutker, J.; Arvas, M.; Carpen, O.; Hinttala, R.; Mannermaa, A.; Aalto-Setala, K.; Kahonen, M.; Makela, J.; Kalviainen, R.; Julkunen, V.; Soininen, H.; Remes, A.; Hiltunen, M.; Peltola, J.; Raivio, M.; Tienari, P.; Rinne, J.; Kallionpaa, R.; Abbasi, A.; Ziemann, A.; Smaoui, N.; Lehtonen, A.; Eaton, S.; Lahdenpera, S.; Bowers, N.; Teng, E.; Xu, F. L.; Addis, L.; Eicher, J.; Li, Q. Q. S.; He, K.; Khramtsova, E.; Farkkila, M.; Koskela, J.; Pikkarainen, S.; Jussila, A.; Kaukinen, K.; Blomster, T.; Kiviniemi, M.; Voutilainen, M.; Lu, T.; McCarthy, L.; Hart, A.; Guan, M. J.; Miller, J.; Kalpala, K.; Miller, M.; Eklund, K.; Palomaki, A.; Isomaki, P.; Pirila, L.; Kaipiainen-Seppa ...; Huhtakangas, J.; Mars, N.; Lertratanakul, A ...; Hochfeld, M.; Gordillo, J. E.; Farias, F.; Bing, N.; Pelkonen, M.; Kauppi, P.; Kankaanranta, Ha ...; Harju, T.; Lahesmaa, R.; Lassi, G.; Chen, H.; Betts, J.; Mishra, R.; Mouded, M.; Ngo, D.; Niiranen, T.; Vaura, F.; Salomaa, V.; Metsarinne, K.; Aittokallio, J.; Hernesniemi, J.; Gordin, D.; Sinisalo, J.; Taskinen, M. R.; Tuomi, T.; Hiltunen, T.; Elliott, A.; Reeve, M. P.; Ruotsalainen, S.; Challis, B.; Chu, A.; Reilly, D.; Mendelson, M.; Parkkinen, J.; Meretoja, T.; Joensuu, H.; Mattson, J.; Salminen, E.; Auranen, A.; Karihtala, P.; Auvinen, P.; Elenius, K.; Pitkanen, E.; Popovic, R.; Schutzman, J.; Kulkarni, D.; Porello, A.; Loboda, A.; Lehtonen, H.; McDonough, S.; Vuoti, S.; Kaarniranta, K.; Turunen, J. A.; Ollila, T.; Uusitalo, H.; Karjalainen, J.; Liu, M. Z.; Loomis, S.; Strauss, E.; Tasanen, K.; Huilaja, L.; Hannula-Jouppi, ...; Salmi, T.; Peltonen, S.; Koulu, L.; Choy, D.; Wu, Y.; Pussinen, P.; Salminen, A.; Salo, T.; Rice, D.; Nieminen, P.; Palotie, U.; Siponen, M.; Suominen, L.; Mantyla, P.; Gursoy, U.; Anttonen, V.; Sipila, K.; Laivuori, H.; Kurra, V.; Kotaniemi-Talone ...; Heikinheimo, O.; Kalliala, I.; Aaltonen, L.; Jokimaa, V.; Vaarasmaki, M.; Morin-Papunen, L ...; Niinimaki, M.; Piltonen, T.; Kivinen, K.; Widen, E.; Tukiainen, T.; Valimaki, N.; Laakkonen, E.; Silven, H.; Arffman, R.; Savukoski, S.; Laisk, T.; Pujol, N.; Kumar, J.; Hovatta, I.; Isometsa, E.; Ollila, H.; Suvisaari, J.; Als, T. D.; Makitie, A.; Bizaki-Vallaskan ...; Toppila-Salmi, S ...; Willberg, T.; Saarentaus, E.; Aarnisalo, A.; Rahikkala, E.; Aittomaki, K.; Aberg, F.; Kurki, M.; Havulinna, A.; Mehtonen, J.; Palta, P.; Hassan, S.; Parolo, P. D.; Zhou, W.; Maasha, M.; Lemmela, S.; Liu, A. X.; Lehisto, A.; Ganna, A.; Llorens, V.; Heyne, H.; Ramo, J.; Rodosthenous, R.; Strausz, S.; Palotie, T.; Palin, K.; Garcia-Tabuenca, ...; Siirtola, H.; Kiiskinen, T.; Lee, J.; Tsuo, K.; Kristiansson, K.; Hyvarinen, K.; Ritari, J.; Pylkas, K.; Karjalainen, M.; Mantere, T.; Kangasniemi, E.; Heikkinen, S.; Pitkanen, N.; Lessard, S.; Terho, P.; Wahlfors, T.; Punkka, E.; Siltanen, S.; Kuopio, T.; Jalanko, A.; Shen, H. Y.; Kajanne, R.; Aavikko, M.; Palin, H.; Linna, M. M.; Kanai, M.; Zheng, Z. L.; Lahtela, L. E.; Kaunisto, M.; Kilpelainen, E.; Sipila, T. P.; Dada, O. A.; Ghazal, A.; Kytola, A.; Weldatsadik, R.; Donner, K.; Loukola, A.; Laiho, P.; Sistonen, T.; Kaiharju, E.; Laukkanen, M.; Jarvensivu, E.; Lahteenmaki, S.; Mannikko, L.; Wong, R.; Toivola, A.; Brunfeldt, M.; Mattsson, H.; Koskelainen, S.; Hiekkalinna, T.; Paajanen, T.; Parn, K.; Kals, M.; Luo, S.; Padmanabhuni, S. ...; Niemi, M.; Gracia-Tabuenca, ...; Helminen, M.; Luukkaala, T.; Vahatalo, I.; Tammerluoto, J.; Smith, S.; Southerington, T ...; Lehto, P.; show less...

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