Journal Article

Identification of common variants associated with human hippocampal and intracranial volumes

Meyer-Lindenberg, Andreas, Holsboer, Florian, Cantor, Rita, Bis, Joshua, Brunner, Han, G, Trabzuni, Daniah, Reinvang, Ivar, Cannon, Dara, D, Bernard, Manon, Harvard University, Dale, Anders, J, University of California [San Francisco] (UC San Francisco) ; University of California (UC), Montreal Neurological Institute and Hospital ; McGill University = Université McGill [Montréal, Canada], Pütz, Benno, Smith, Albert, V, Universität Greifswald = University of Greifswald, Università degli Studi di Salermo ; Università degli Studi di Salerno = University of Salerno (UNISA), Roffman, Joshua, L, Boomsma, Dorret, Fagerness, Jesen, Moses, Eric, K, Montgomery, Grant, W, Seiferth, Nina, Mattheisen, Manuel, Wright, Margaret, Deary, Ian, Westlye, Lars, University of Toronto, Walter, Henrik, Olvera, Rene, L, van den Heuvel, Martijn, D, Nöthen, Markus, M, Broad Institute of MIT and Harvard (BROAD INSTITUTE) ; Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], O'Brien, Carol, Brown, Andrew, A, Vern

2012

Overview

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group US
• Subject: 631/208/205/2138 / 631/208/480 / 631/208/726/649 / Agriculture / Anatomie (cytologie, histologie, embryologie...) & physiologie / Anatomy (cytology, histology, embryology...) & physiology / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Body size / Brain / Brain - physiopathology / Cancer Research / Chromosomes, Human, Pair 12 - genetics / Fundamental and applied biological sciences. Psychology / Gene Function / Genealogy / Genetic aspects / Genetic Loci / Genetic Markers / Genetic variance / Genetic variation / Genetics / Genetics & genetic processes / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Genomes / Génétique & processus génétiques / Haplotypes / Head / Hippocampus (Brain) / Hippocampus - physiopathology / Human Genetics / Humans / Identification and classification / letter / Life Sciences / Meta-analysis / Meta-Analysis as Topic / Neuroimaging / Neurology / Neurons and Cognition / Polymorphism, Single Nucleotide - genetics / Quality control / Sciences du vivant / Statistical analysis / Studies