Genetic variants for head size share genes and pathways with cancer

Maria J Knol; Raymond A Poot; Tavia E Evans; Claudia L Satizabal; Aniket Mishra; Muralidharan Sargurupremraj; Sandra van der Auwera; Marie-Gabrielle Duperron; Xueqiu Jian; Isabel C Hostettler; Dianne H K van Dam-Nolen; Sander Lamballais; Mikolaj A Pawlak; Cora E Lewis; Amaia Carrion-Castillo; Theo G M van Erp; Céline S Reinbold; Jean Shin; Markus Scholz; Asta K Håberg; Anders Kämpe; Gloria H Y Li; Reut Avinun; Joshua R Atkins; Fang-Chi Hsu; Alyssa R Amod; Max Lam; Ami Tsuchida; Mariël W A Teunissen; Nil Aygün; Yash Patel; Dan Liang; Alexa S Beiser; Frauke Beyer; Joshua C Bis; Daniel Bos; R Nick Bryan; Robin Bülow; Svenja Caspers; Gwenaëlle Catheline; Charlotte A M Cecil; Shareefa Dalvie; Jean-François Dartigues; Charles DeCarli; Maria Enlund-Cerullo; Judith M Ford; Barbara Franke; Barry I Freedman; Nele Friedrich; Melissa J Green; Han Brunner; Hieab H. H. Adams; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium; ENIGMA Consortium

doi:10.1016/j.xcrm.2024.101529

Genetic variants for head size share genes and pathways with cancer

Maria J Knol, Raymond A Poot, Tavia E Evans, Claudia L Satizabal, Aniket Mishra, Muralidharan Sargurupremraj, Sandra van der Auwera, Marie-Gabrielle Duperron, Xueqiu Jian, Isabel C Hostettler, Dianne H K van Dam-Nolen, Sander Lamballais, Mikolaj A Pawlak, Cora E Lewis, Amaia Carrion-Castillo, Theo G M van Erp, Céline S Reinbold, Jean Shin, Markus Scholz, Asta K HåbergAnders Kämpe, Gloria H Y Li, Reut Avinun, Joshua R Atkins, Fang-Chi Hsu, Alyssa R Amod, Max Lam, Ami Tsuchida, Mariël W A Teunissen, Nil Aygün, Yash Patel, Dan Liang, Alexa S Beiser, Frauke Beyer, Joshua C Bis, Daniel Bos, R Nick Bryan, Robin Bülow, Svenja Caspers, Gwenaëlle Catheline, Charlotte A M Cecil, Shareefa Dalvie, Jean-François Dartigues, Charles DeCarli, Maria Enlund-Cerullo, Judith M Ford, Barbara Franke, Barry I Freedman, Nele Friedrich, Melissa J Green, Han Brunner, Hieab H. H. Adams^*, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, ENIGMA Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	101529
Journal	Cell Reports Medicine
Volume	5
Issue number	5
Early online date	3 May 2024
DOIs	https://doi.org/10.1016/j.xcrm.2024.101529
Publication status	Published - 21 May 2024

Keywords

cancer
genetics
genome-wide association study
head circumference
head size
intracranial volume
meta-analysis

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10.1016/j.xcrm.2024.101529Licence: CC BY

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Knol, M. J., Poot, R. A., Evans, T. E., Satizabal, C. L., Mishra, A., Sargurupremraj, M., van der Auwera, S., Duperron, M.-G., Jian, X., Hostettler, I. C., van Dam-Nolen, D. H. K., Lamballais, S., Pawlak, M. A., Lewis, C. E., Carrion-Castillo, A., van Erp, T. G. M., Reinbold, C. S., Shin, J., Scholz, M., ... ENIGMA Consortium (2024). Genetic variants for head size share genes and pathways with cancer. Cell Reports Medicine, 5(5), Article 101529. https://doi.org/10.1016/j.xcrm.2024.101529

@article{2ab8e8daeb68434f9b78b9fab72e2202,

title = "Genetic variants for head size share genes and pathways with cancer",

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.",

keywords = "cancer, genetics, genome-wide association study, head circumference, head size, intracranial volume, meta-analysis",

author = "Knol, {Maria J} and Poot, {Raymond A} and Evans, {Tavia E} and Satizabal, {Claudia L} and Aniket Mishra and Muralidharan Sargurupremraj and {van der Auwera}, Sandra and Marie-Gabrielle Duperron and Xueqiu Jian and Hostettler, {Isabel C} and {van Dam-Nolen}, {Dianne H K} and Sander Lamballais and Pawlak, {Mikolaj A} and Lewis, {Cora E} and Amaia Carrion-Castillo and {van Erp}, {Theo G M} and Reinbold, {C{\'e}line S} and Jean Shin and Markus Scholz and H{\aa}berg, {Asta K} and Anders K{\"a}mpe and Li, {Gloria H Y} and Reut Avinun and Atkins, {Joshua R} and Fang-Chi Hsu and Amod, {Alyssa R} and Max Lam and Ami Tsuchida and Teunissen, {Mari{\"e}l W A} and Nil Ayg{\"u}n and Yash Patel and Dan Liang and Beiser, {Alexa S} and Frauke Beyer and Bis, {Joshua C} and Daniel Bos and Bryan, {R Nick} and Robin B{\"u}low and Svenja Caspers and Gwena{\"e}lle Catheline and Cecil, {Charlotte A M} and Shareefa Dalvie and Jean-Fran{\c c}ois Dartigues and Charles DeCarli and Maria Enlund-Cerullo and Ford, {Judith M} and Barbara Franke and Freedman, {Barry I} and Nele Friedrich and Green, {Melissa J} and Han Brunner and Adams, {Hieab H. H.} and {Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium} and {ENIGMA Consortium}",

year = "2024",

month = may,

day = "21",

doi = "10.1016/j.xcrm.2024.101529",

language = "English",

volume = "5",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "5",

}

Knol, MJ, Poot, RA, Evans, TE, Satizabal, CL, Mishra, A, Sargurupremraj, M, van der Auwera, S, Duperron, M-G, Jian, X, Hostettler, IC, van Dam-Nolen, DHK, Lamballais, S, Pawlak, MA, Lewis, CE, Carrion-Castillo, A, van Erp, TGM, Reinbold, CS, Shin, J, Scholz, M, Håberg, AK, Kämpe, A, Li, GHY, Avinun, R, Atkins, JR, Hsu, F-C, Amod, AR, Lam, M, Tsuchida, A, Teunissen, MWA, Aygün, N, Patel, Y, Liang, D, Beiser, AS, Beyer, F, Bis, JC, Bos, D, Bryan, RN, Bülow, R, Caspers, S, Catheline, G, Cecil, CAM, Dalvie, S, Dartigues, J-F, DeCarli, C, Enlund-Cerullo, M, Ford, JM, Franke, B, Freedman, BI, Friedrich, N, Green, MJ, Brunner, H, Adams, HHH, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium & ENIGMA Consortium 2024, 'Genetic variants for head size share genes and pathways with cancer', Cell Reports Medicine, vol. 5, no. 5, 101529. https://doi.org/10.1016/j.xcrm.2024.101529

TY - JOUR

T1 - Genetic variants for head size share genes and pathways with cancer

AU - Knol, Maria J

AU - Poot, Raymond A

AU - Evans, Tavia E

AU - Satizabal, Claudia L

AU - Mishra, Aniket

AU - Sargurupremraj, Muralidharan

AU - van der Auwera, Sandra

AU - Duperron, Marie-Gabrielle

AU - Jian, Xueqiu

AU - Hostettler, Isabel C

AU - van Dam-Nolen, Dianne H K

AU - Lamballais, Sander

AU - Pawlak, Mikolaj A

AU - Lewis, Cora E

AU - Carrion-Castillo, Amaia

AU - van Erp, Theo G M

AU - Reinbold, Céline S

AU - Shin, Jean

AU - Scholz, Markus

AU - Håberg, Asta K

AU - Kämpe, Anders

AU - Li, Gloria H Y

AU - Avinun, Reut

AU - Atkins, Joshua R

AU - Hsu, Fang-Chi

AU - Amod, Alyssa R

AU - Lam, Max

AU - Tsuchida, Ami

AU - Teunissen, Mariël W A

AU - Aygün, Nil

AU - Patel, Yash

AU - Liang, Dan

AU - Beiser, Alexa S

AU - Beyer, Frauke

AU - Bis, Joshua C

AU - Bos, Daniel

AU - Bryan, R Nick

AU - Bülow, Robin

AU - Caspers, Svenja

AU - Catheline, Gwenaëlle

AU - Cecil, Charlotte A M

AU - Dalvie, Shareefa

AU - Dartigues, Jean-François

AU - DeCarli, Charles

AU - Enlund-Cerullo, Maria

AU - Ford, Judith M

AU - Franke, Barbara

AU - Freedman, Barry I

AU - Friedrich, Nele

AU - Green, Melissa J

AU - Brunner, Han

AU - Adams, Hieab H. H.

AU - Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

AU - ENIGMA Consortium

PY - 2024/5/21

Y1 - 2024/5/21

N2 - 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.

AB - 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.

KW - cancer

KW - genetics

KW - genome-wide association study

KW - head circumference

KW - head size

KW - intracranial volume

KW - meta-analysis

U2 - 10.1016/j.xcrm.2024.101529

DO - 10.1016/j.xcrm.2024.101529

M3 - Article

SN - 2666-3791

VL - 5

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 5

M1 - 101529

ER -

Genetic variants for head size share genes and pathways with cancer

Abstract

Keywords

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