Genetic variants for head size share genes and pathways with cancer.

Publication

Genetic variants for head size share genes and pathways with cancer.

Journal Paper/Review - May 3, 2024

Knol Maria J, Poot Raymond A, Evans Tavia E, Satizabal Claudia L, Mishra Aniket, Sargurupremraj Muralidharan, van der Auwera Sandra, Duperron Marie-Gabrielle, Jian Xueqiu, Hostettler Isabel, van Dam-Nolen Dianne H K, Lamballais Sander, Pawlak Mikolaj A, Lewis Cora E, Carrion-Castillo Amaia, van Erp Theo G M, Reinbold Céline S, Shin Jean, Scholz Markus, Håberg Asta K, Kämpe Anders, Li Gloria H Y, Avinun Reut, Atkins Joshua R, Hsu Fang-Chi, Amod AlyR, Lam Max, Tsuchida Ami, Teunissen Mariël W A, Aygün Nil, Patel Yash, Liang Dan, Beiser Alexa S, Beyer Frauke, Bis Joshua C, Bos Daniel, Bryan R Nick, Bülow Robin, Caspers Svenja, Catheline Gwenaëlle, Cecil Charlotte A M, Dalvie Shareefa, Dartigues Jean-François, DeCarli Charles, Enlund-Cerullo Maria, Ford Judith M, Franke Barbara, Freedman Barry I, Friedrich Nele, Green MeliJ, Haworth Simon, Helmer Catherine, Hoffmann Per, Homuth Georg, Ikram Mohammad Arfan, Jack Clifford R, Jahanshad Neda, Jockwitz Christiane, Kamatani Yoichiro, Knodt Annchen R, Li Shuo, Lim Keane, Longstreth W T, Macciardi Fabio, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, Mäkitie Outi, Mazoyer Bernard, Medland Sarah E, Miyamoto Susumu, Moebus Susanne, Mosley Thomas H, Muetzel Ryan, Mühleisen Thomas W, Nagata Manabu, Nakahara Soichiro, Palmer Nicholette D, Pausova Zdenka, Preda Adrian, Quidé Yann, Reay William R, Roshchupkin Gennady V, Schmidt Reinhold E, Schreiner Pamela J, Setoh Kazuya, Shapland Chin Yang, Sidney Stephen, St Pourcain Beate, Stein Jason L, Tabara Yasuharu, Teumer Alexander, Uhlmann Anne, van der Lugt Aad, Vernooij Meike W, Werring David J, Windham B Gwen, Witte A Veronica, Wittfeld Katharina, Yang Qiong, Yoshida Kazumichi, Brunner Han G, Le Grand Quentin, Sim Kang, Stein Dan J, Bowden Donald W, Cairns Murray J, Hariri Ahmad R, Cheung Ching-Lung, Andersson Sture, Villringer Arno, Paus Tomas, Cichon Sven, Calhoun Vince D, Crivello Fabrice, Launer Lenore J, White Tonya, Koudstaal Peter J, Houlden Henry, Fornage Myriam, Matsuda Fumihiko, Grabe Hans Jörgen, Debette Stephanie, Thompson Paul M, Seshadri Sudha, Adams Hieab H H

Citation

Knol M, Poot R, Evans T, Satizabal C, Mishra A, Sargurupremraj M, van der Auwera S, Duperron M, Jian X, Hostettler I, van Dam-Nolen D, Lamballais S, Pawlak M, Lewis C, Carrion-Castillo A, van Erp T, Reinbold C, Shin J, Scholz M, Håberg A, Kämpe A, Li G, Avinun R, Atkins J, Hsu F, Amod A, Lam M, Tsuchida A, Teunissen M, Aygün N, Patel Y, Liang D, Beiser A, Beyer F, Bis J, Bos D, Bryan R, Bülow R, Caspers S, Catheline G, Cecil C, Dalvie S, Dartigues J, DeCarli C, Enlund-Cerullo M, Ford J, Franke B, Freedman B, Friedrich N, Green M, Haworth S, Helmer C, Hoffmann P, Homuth G, Ikram M, Jack C, Jahanshad N, Jockwitz C, Kamatani Y, Knodt A, Li S, Lim K, Longstreth W, Macciardi F, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium, Mäkitie O, Mazoyer B, Medland S, Miyamoto S, Moebus S, Mosley T, Muetzel R, Mühleisen T, Nagata M, Nakahara S, Palmer N, Pausova Z, Preda A, Quidé Y, Reay W, Roshchupkin G, Schmidt R, Schreiner P, Setoh K, Shapland C, Sidney S, St Pourcain B, Stein J, Tabara Y, Teumer A, Uhlmann A, van der Lugt A, Vernooij M, Werring D, Windham B, Witte A, Wittfeld K, Yang Q, Yoshida K, Brunner H, Le Grand Q, Sim K, Stein D, Bowden D, Cairns M, Hariri A, Cheung C, Andersson S, Villringer A, Paus T, Cichon S, Calhoun V, Crivello F, Launer L, White T, Koudstaal P, Houlden H, Fornage M, Matsuda F, Grabe H, Debette S, Thompson P, Seshadri S, Adams H. Genetic variants for head size share genes and pathways with cancer. Cell Rep Med 2024:101529.

Type

Journal Paper/Review (English)

Journal

Cell Rep Med 2024

Publication Date

May 3, 2024

Issn Electronic

2666-3791

Pages

101529

Brief description/objective

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.