1. Genome-wide significant linkage of schizophrenia-related neuroanatomical trait to 12q24
- Author
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Samuel R. Mathias, Cota Navin Gupta, Emma Knowles, Marcio Almeida, Rene L. Olvera, Ravi Duggirala, Thomas D. Dyer, Harald H H Göring, Melanie A. Carless, Vince D. Calhoun, David C. Glahn, D. Reese McKay, Laura Almasy, Joanne E. Curran, Peter T. Fox, Jack W. Kent, Peter Kochunov, Emma Sprooten, John Blangero, and Jessica A. Turner
- Subjects
Adult ,Male ,Adolescent ,Genetic Linkage ,Population ,Prefrontal Cortex ,Genome-wide association study ,Biology ,Quantitative trait locus ,behavioral disciplines and activities ,Article ,Young Adult ,Cellular and Molecular Neuroscience ,Cognition ,Genetic linkage ,Mexican Americans ,Genetic variation ,Humans ,Gray Matter ,education ,Prefrontal cortex ,Genetics (clinical) ,Psychiatric genetics ,Aged ,Aged, 80 and over ,Cerebral Cortex ,education.field_of_study ,Chromosomes, Human, Pair 12 ,Middle Aged ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,nervous system ,Multivariate Analysis ,Schizophrenia ,Female ,Insula ,Neuroscience ,psychological phenomena and processes ,Genome-Wide Association Study - Abstract
The insula and medial prefrontal cortex (mPFC) share functional, histological, transcriptional, and developmental characteristics, and they serve higher cognitive functions of theoretical relevance to schizophrenia and related disorders. Meta-analyses and multivariate analysis of structural magnetic resonance imaging (MRI) scans indicate that gray matter density and volume reductions in schizophrenia are the most consistent and pronounced in a network primarily composed of the insula and mPFC. We used source-based morphometry, a multivariate technique optimized for structural MRI, in a large sample of randomly ascertained pedigrees (N = 887) to derive an insula-mPFC component and to investigate its genetic determinants. Firstly, we replicated the insula-mPFC gray matter component as an independent source of gray matter variation in the general population, and verified its relevance to schizophrenia in an independent case-control sample. Secondly, we showed that the neuroanatomical variation defined by this component is largely determined by additive genetic variation (h(2) = 0.59), and genome-wide linkage analysis resulted in a significant linkage peak at 12q24 (LOD = 3.76). This region has been of significant interest to psychiatric genetics as it contains the Darier's disease locus and other proposed susceptibility genes (e.g., DAO, NOS1), and it has been linked to affective disorders and schizophrenia in multiple populations. Thus, in conjunction with previous clinical studies, our data imply that one or more psychiatric risk variants at 12q24 are co-inherited with reductions in mPFC and insula gray matter concentration. © 2015 Wiley Periodicals, Inc.
- Published
- 2015