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  Genetic variants for head size share genes and pathways with cancer

Knol, M. J., Poot, R. A., Evans, T. E., Satizabal, C. L., Mishra, A., Sargurupremraj, M., et al. (2024). Genetic variants for head size share genes and pathways with cancer. Cell Reports Medicine. Advance online publication. doi:10.1016/j.xcrm.2024.101529.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000F-3BE6-C Version Permalink: https://hdl.handle.net/21.11116/0000-000F-5244-8
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© 2024 The Author(s). Published by Elsevier Inc This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article.
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Knol, Maria J.1, Author
Poot, Raymond A.1, Author
Evans, Tavia E.1, Author
Satizabal, Claudia L.2, 3, 4, Author
Mishra, Aniket5, Author
Sargurupremraj, Muralidharan2, Author
Van der Auwera, Sandra6, 7, Author
Duperron, Marie-Gabrielle5, Author
Jian, Xueqiu8, Author
Hostettler, Isabel C.9, 10, 11, Author
Van Dam-Nolen, Dianne H. K.1, Author
Lamballais, Sander1, Author
Pawlak, Mikolaj A.12, 13, Author
Lewis, Cora E.14, Author
Carrion Castillo, Amaia15, Author           
Van Erp, Theo G. M.16, Author
Reinbold, Celine S.17, 18, 19, Author
Shin, Jean20, Author
Sholz, Markus21, 22, Author
Håberg, Asta K.23, 24, Author
Kämpe, Anders25, 26, AuthorLi, Gloria H. Y.27, AuthorAvinun, Reut28, AuthorAtkins, Joshua R.29, 30, AuthorHsu, Fang-Chi31, AuthorAmod, Alyssa R.32, AuthorLam, Max33, 34, AuthorTsuchida, Ami5, AuthorTeunissen, Mariël W. A.13, 35, AuthorAygün, Nil36, AuthorPatel, Yash20, AuthorLiang, Dan36, AuthorBeiser, Alexa S.3, 4, AuthorBeyer, Frauke21, 37, 38, AuthorBis, Joshua C.39, AuthorBos, Daniel1, AuthorBryan, R. Nick40, AuthorBülow, Robin6, AuthorCaspers, Svenja41, 42, AuthorCatheline, Gwenaëlle 5, AuthorCecil, Charlotte A. M.1, AuthorDalvie, Shareefa32, AuthorDartigues, Jean-Francois5, AuthorDeCarli, Charles43, AuthorEnlund-Cerullo, Maria44, AuthorFord, Judith M.45, 46, AuthorFranke, Barbara13, 47, AuthorFreedman, Barry I.31, AuthorFriedrich, Nele6, AuthorGreen, Melissa J.48, 49, AuthorHaworth, Simon50, AuthorHelmer, Catherine5, AuthorHoffmann, Per17, 18, 51, AuthorHomuth, Georg6, AuthorIkram, M. Kamran1, AuthorJack, Clifford R.52, AuthorJahanshad, Neda53, AuthorJockwitz, Christiane41, 54, AuthorKamatani, Yoichiro55, AuthorKnodt, Annchen R.28, AuthorLi, Shuo4, AuthorLim, Keane33, AuthorLongstreth, W. T. 39, AuthorMacciardi, Fabio16, AuthorThe Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Author              The Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium, Author              Mäkitie, Outi25, 26, 44, AuthorMazoyer, Bernard5, AuthorMedland, Sarah E.56, 57, AuthorMiyamoto, Susumu55, AuthorMoebus, Susanne58, AuthorMosley, Thomas H.59, 60, AuthorMuetzel, Ryan1, AuthorMühleisen, Thomas W.17, 41, 42, AuthorNagata, Manabu55, AuthorNakahara, Soichiro16, AuthorPalmer, Nicholette D.31, AuthorPausova, Zdenka20, AuthorPreda, Adrian16, AuthorQuidé, Yann48, 49, AuthorReay, William R.29, 30, AuthorRoshchupkin, Gennady V.1, AuthorSchmidt, Reinhold61, AuthorSchreiner, Pamela J.62, AuthorSetoh, Kazuya55, AuthorShapland, Chin Yang15, 50, Author           Sidney, Stephen63, AuthorSt Pourcain, Beate15, 47, 50, 64, Author           Stein, Jason L.36, AuthorTabara, Yasuharu55, AuthorTeumer, Alexander6, AuthorUhlmann, Anne32, AuthorVan de Lught, Aad1, AuthorVernooij, Meike W.1, AuthorWerring, David J.9, AuthorWindham, B. Gwen59, 60, AuthorWitte, A. Veronica37, 38, AuthorWittfeld, Katharina6, 7, AuthorYang, Qiong4, AuthorYoshida, Kazumichi55, AuthorBrunner, Han G.13, 65, AuthorLe Grand, Quentin5, AuthorSim, Kang33, 34, AuthorStein, Dan J.32, 66, AuthorBowden, Donald W.31, AuthorCairns, Murray J.29, 30, AuthorHariri, Ahmad R.28, AuthorCheung, Ching-Lung33, 34, AuthorAndersson, Sture44, AuthorVillringer, Arno37, 38, AuthorPaus, Tomas67, 68, AuthorChichon, Sven17, 18, 41, AuthorCalhoun, Vince D.69, AuthorCrivello, Fabrice5, AuthorLauner, Lenore J.70, AuthorWhite, Tonya1, AuthorKoudstaal, Peter J.1, AuthorHoulden, Henry9, AuthorFornage, Myriam8, AuthorMatsuda, Fumihiko55, AuthorGrabe, Hans J.6, AuthorIkram, M. Arfan1, AuthorDebette, Stephanie5, AuthorThompson, Paul M.53, AuthorSeshadri, Sudha2, 3, 4, AuthorAdams, Hieab H. H.13, Author more..
Affiliations:
1Erasmus MC, Rotterdam, The Netherlands, ou_persistent22              
2The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA, ou_persistent22              
3The Framingham Heart Study, Framingham, MA, USA, ou_persistent22              
4Boston University School of Medicine, Boston, MA, USA, ou_persistent22              
5University of Bordeaux, Bordeaux, France, ou_persistent22              
6University Medicine Greifswald, Greifswald, Germany, ou_persistent22              
7German Centre of Neurodegenerative Diseases (DZNE), Greifswald, Germany, ou_persistent22              
8University of Texas Health Science Center at Houston, Houston, TX, USA, ou_persistent22              
9University College London, London, UK, ou_persistent22              
10University of Munich, Munich, Germany, ou_persistent22              
11Cantonal Hospital St. Gallen, St. Gallen, Switzerland, ou_persistent22              
12Poznań University of Medical Sciences, Poznań, Poland, ou_persistent22              
13Radboud University Medical Center, Nijmegen, The Netherlands, ou_persistent22              
14University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA, ou_persistent22              
15Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, Nijmegen, NL, ou_792549              
16University of California, Irvine, Irvine, CA, USA, ou_persistent22              
17University of Basel, Basel, Switzerland, ou_persistent22              
18University Hospital Basel, Basel, Switzerland, ou_persistent22              
19Zurich University of Applied Sciences, Wädenswil, Switzerland, ou_persistent22              
20University of Toronto, Toronto, Canada, ou_persistent22              
21University of Leipzig, Leipzig, Germany, ou_persistent22              
22LIFE Research Center for Civilization Disease, Leipzig, Germany, ou_persistent22              
23Norwegian University of Science and Technology (NTNU), Trondheim, Trondheim, Norway, ou_persistent22              
24St. Olavs University Hospital, Trondheim, Norway, ou_persistent22              
25Karolinska Institutet, Stockholm, Sweden, ou_persistent22              
26Karolinska University Hospital, Stockholm, Sweden, ou_persistent22              
27The University of Hong Kong, Hong Kong, China, ou_persistent22              
28Duke University, Durham, Durham, NC, USA, ou_persistent22              
29The University of Newcastle, Callaghan, Australia, ou_persistent22              
30Hunter Medical Research Institute, Newcastle, Australia, ou_persistent22              
31Wake Forest University School of Medicine, Winston-Salem, NC, USA, ou_persistent22              
32TU Dresden, Dresden, Germany, ou_persistent22              
33Institute of Mental Health, Singapore, Singapore, Singapore, ou_persistent22              
34Nanyang Technological University, Singapore, Singapore, ou_persistent22              
35Maastricht University Medical Center, Maastricht, The Netherlands, ou_persistent22              
36University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, ou_persistent22              
37Max Planck Institute for Cognitive and Brain Sciences, Leipzig, Germany, ou_persistent22              
38University Hospital Leipzig, Leipzig, Germany, ou_persistent22              
39University of Washington, Seattle, Seattle, WA, USA, ou_persistent22              
40University of Pennsylvania, Philadelphia, PA, USA, ou_persistent22              
41Research Centre Jülich, Jülich, Germany, ou_persistent22              
42Heinrich Heine University Düsseldorf, Düsseldorf, Germany, ou_persistent22              
43University of California at Davis, Sacramento, CA, USA, ou_persistent22              
44University of Helsinki , Helsinki, Finland, ou_persistent22              
45San Francisco Veterans Administration Medical Center, San Francisco, CA, USA, ou_persistent22              
46University of California, San Francisco, CA, USA, ou_persistent22              
47Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              
48University of New South Wales, Sydney, Australia, ou_persistent22              
49Neuroscience Research Australia, Sydney, Australia, ou_persistent22              
50University of Bristol, Bristol, UK, ou_persistent22              
51University of Bonn Medical School, Bonn, Germany, ou_persistent22              
52Mayo Clinic, Rochester, Rochester, MN, USA, ou_persistent22              
53Keck USC School of Medicine, Los Angeles, CA, USA, ou_persistent22              
54Aachen University, Aachen, Germany, ou_persistent22              
55Kyoto University Graduate School of Medicine, Kyoto, Japan, ou_persistent22              
56QIMR Berghofer Medical Research Institute, Brisbane, Australia, ou_persistent22              
57University of Queensland, Brisbane, Australia, ou_persistent22              
58University of Duisburg-Essen, Essen, Germany, ou_persistent22              
59University of Mississippi Medical Center, Jackson, MS, USA, ou_persistent22              
60Memory Impairment and Neurodegenerative Dementia (MIND) Center, Jackson, MS, USA, ou_persistent22              
61Medical University of Graz, Graz, Austria, ou_persistent22              
62University of Minnesota School of Public Health, Minneapolis, MN, USA, ou_persistent22              
63Kaiser Permanente Division of Research, Oakland, CA, USA, ou_persistent22              
64Population genetics of human communication, MPI for Psycholinguistics, Max Planck Society, ou_2579694              
65Maastricht University, Maastricht, The Netherlands, ou_persistent22              
66University of Cape Town, Cape Town, South Africa, ou_persistent22              
67University of Montreal, Montreal, Canada, ou_persistent22              
68McGill University, Montreal, Canada, ou_persistent22              
69Georgia Tech, Atlanta, GA, USA, ou_persistent22              
70The National Institutes of Health, Bethesda, MD, USA, ou_persistent22              

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 Abstract: The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

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Language(s): eng - English
 Dates: 20242024-05-03
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.xcrm.2024.101529
 Degree: -

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Title: Cell Reports Medicine. Advance online publication
  Abbreviation : CELL REP MED
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: CoNE: https://pure.mpg.de/cone/journals/resource/2666-3791