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Novel genetic loci associated with hippocampal volume

Article scientifique 2017 Anglais

Résumé

Abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes ( ASTN2 , DPP4 and MAST4 ) and one is found 200 kb upstream of SHH . A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer’s disease ( r g =−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

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Hibar, D., Adams, H., Jahanshad, N., Chauhan, G., Stein, J., Hofer, E., Rentería, M., Bis, J., Vásquez, A., Ikram, M., Ikram, M., Desrivières, S., Vernooij, M., Abramović, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B., Armstrong, N., Athanasiu, L., Axelsson, T., Beecham, A., Beiser, A., Bernard, M., Blanton, S., Bohlken, M., Boks, M., Bralten, J., Brickman, A., Carmichael, O., Chakravarty, M., Chen, Q., Ching, C., Chouraki, V., Cuéllar-Partida, G., Crivello, F., Braber, A., Doan, N., Ehrlich, S., Giddaluru, S., Goldman, A., Gottesman, R., Grimm, O., Griswold, M., Guadalupe, T., Gutman, B., Haß, J., Haukvik, U., Hoehn, D., Holmes, A., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K., Karbalai, N., Kasperavičiūtė, D., Kim, S., Klein, M., Kraemer, B., Lee, P., Liewald, D., Lopez, L., Luciano, M., Macare, C., Marquand, A., Matarin, M., Mather, K., Mattheisen, M., McKay, D., Milaneschi, Y., Maniega, S., Nho, K., Nugent, A., Nyquist, P., Loohuis, L., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Pütz, B., Adaikalavan, R., Richards, J., Risacher, S., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E., Royle, N., Rundek, T., Sämann, P., Saremi, A., Satizábal, C., Schmaal, L., Schork, A., Shin, J., Shumskaya, E., Smith, A., Sprooten, E., Strike, L. (2017). Novel genetic loci associated with hippocampal volume. https://doi.org/10.1038/ncomms13624

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Auteur(s)

Derrek P. Hibar Hieab H.H. Adams Neda Jahanshad Ganesh Chauhan Jason L. Stein Edith Hofer Miguel E. Rentería Joshua C. Bis Alejandro Arias Vásquez M. Kamran Ikram Sylvane Desrivières Meike W. Vernooij Lucija Abramović Saud Alhusaini Najaf Amin Micael Andersson Konstantinos Arfanakis Benjamin S. Aribisala Nicola J. Armstrong Lavinia Athanasiu Tomas Axelsson Ashley H. Beecham Alexa Beiser Manon Bernard Susan H. Blanton Marc M. Bohlken Marco P. Boks Janita Bralten Adam M. Brickman Owen Carmichael M. Mallar Chakravarty Qiang Chen Christopher R. K. Ching Vincent Chouraki Gabriel Cuéllar-Partida Fabrice Crivello Anouk den Braber Nhat Trung Doan Stefan Ehrlich Sudheer Giddaluru Aaron L. Goldman Rebecca F. Gottesman Oliver Grimm M E Griswold Tulio Guadalupe Boris A. Gutman Johanna Haß Unn K. Haukvik David Hoehn Avram J. Holmes Martine Hoogman Deborah Janowitz Tianye Jia Kjetil N. Jørgensen Nazanin Karbalai Dalia Kasperavičiūtė Sungeun Kim Marieke Klein Bernd Kraemer Phil H. Lee David C. M. Liewald Lorna M. Lopez Michelle Luciano Christine Macare André F. Marquand Mar Matarin Karen A. Mather Manuel Mattheisen David R. McKay Yuri Milaneschi Susana Muñoz Maniega Kwangsik Nho Allison C. Nugent Paul Nyquist Loes M. Olde Loohuis Jaap Oosterlaan Martina Papmeyer Lukas Pirpamer Benno Pütz Ramasamy Adaikalavan Jennifer S. Richards Shannon L. Risacher Roberto Roiz-Santiañez Nanda Rommelse Stefan Ropele Emma Rose Natalie A. Royle Tatjana Rundek Philipp G. Sämann Arvin Saremi Claudia L. Satizábal Lianne Schmaal Andrew J. Schork Jean Shin Elena Shumskaya Albert V. Smith Emma Sprooten Lachlan T. Strike

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