Novel genetic loci underlying human intracranial volume identified through genome-wide association

Hieab H. H. Adams, Derrek P. Hibar, Vincent Chouraki, Jason L. Stein, Paul A. Nyquist, Miguel E. Renteria, Stella Trompet, Alejandro Arias-Vasquez, Sudha Seshadri, Sylvane Desrivieres, Ashley H. Beecham, Neda Jahanshad, Katharine Wittfeld, Sven J. Van der Lee, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. AribisalaNicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Alexa Beiser, Manon Bernard, Joshua C. Bis, Laura M. E. Blanken, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Ganesh Chauhan, Qiang Chen, Christopher R. K. Ching, Gabriel Cuellar-Partida, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Jennifer S. Richards, Lianne Schmaal, Albert V. Smith, Dennis Van der Meer, Daan Van Rooij, Catharina A. Hartman, Pieter J. Hoekstra, Brenda W. J. H. Penninx, Marie Jose Van Tol, Alzheimer's Dis Neuroimaging Initi, EPIGEN, IMAGEN, SYS

OnderzoeksoutputAcademicpeer review

134 Citaten (Scopus)


Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Originele taal-2English
Pagina's (van-tot)1569-1582
Aantal pagina's14
TijdschriftNature neuroscience
Nummer van het tijdschrift12
StatusPublished - dec-2016

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