Distinct genetic influences on cortical surface area and cortical thickness.

Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.

[1]  R. Nichols,et al.  The diagnosis of twin zygosity. , 1966, Acta genetica et statistica medica.

[2]  N. Martin,et al.  Model-fitting approaches to the analysis of human behaviour , 1978, Heredity.

[3]  J Goldberg,et al.  The Vietnam Era Twin (VET) Registry: method of construction. , 1987, Acta geneticae medicae et gemellologiae.

[4]  P. Rakic.  Specification of cerebral cortical areas. , 1988, Science.

[5]  John P. Rice,et al.  Determining zygosity in the Vietnam Era Twin Registry: an approach using questionnaires , 1989, Clinical genetics.

[6]  W R True,et al.  The Vietnam Era Twin Registry: a resource for medical research. , 1990, Public health reports.

[7]  A. Thapar,et al.  Methodology for Genetic Studies of Twins and Families , 1993 .

[8]  P. Rakic.  A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution , 1995, Trends in Neurosciences.

[9]  Karl J. Friston,et al.  A Voxel-Based Method for the Statistical Analysis of Gray and White Matter Density Applied to Schizophrenia , 1995, NeuroImage.

[10]  B. Pakkenberg,et al.  Neocortical neuron number in humans: Effect of sex and age , 1997, The Journal of comparative neurology.

[11]  V. Mountcastle.  The columnar organization of the neocortex. , 1997, Brain : a journal of neurology.

[12]  R Derom,et al.  Validation of a Telephone Zygosity Questionnaire in Twins of Known Zygosity , 1998, Behavior genetics.

[13]  Anders M. Dale,et al.  Cortical Surface-Based Analysis I. Segmentation and Surface Reconstruction , 1999, NeuroImage.

[14]  Alan C. Evans,et al.  Brain development during childhood and adolescence: a longitudinal MRI study , 1999, Nature Neuroscience.

[15]  A. Dale,et al.  Cortical Surface-Based Analysis II: Inflation, Flattening, and a Surface-Based Coordinate System , 1999, NeuroImage.

[16]  D. O'Leary,et al.  Regulation of area identity in the mammalian neocortex by Emx2 and Pax6. , 2000, Science.

[17]  R. Murray,et al.  Meta-analysis of regional brain volumes in schizophrenia. , 2000, The American journal of psychiatry.

[18]  A M Dale,et al.  Measuring the thickness of the human cerebral cortex from magnetic resonance images. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Luca Muzio,et al.  Area identity shifts in the early cerebral cortex of Emx2−/− mutant mice , 2000, Nature Neuroscience.

[20]  Tyrone D. Cannon,et al.  Genetic influences on brain structure , 2001, Nature Neuroscience.

[21]  C. Fennema-Notestine,et al.  Effects of age on tissues and regions of the cerebrum and cerebellum , 2001, Neurobiology of Aging.

[22]  R. Kahn,et al.  The association between brain volume and intelligence is of genetic origin , 2002, Nature Neuroscience.

[23]  Charles DeCarli,et al.  Quantitative genetic modeling of regional brain volumes and cognitive performance in older male twins , 2002, Biological Psychology.

[24]  P. Sullivan,et al.  Evaluation of Analyses of Univariate Discrete Twin Data , 2002, Behavior Genetics.

[25]  Edward J Boyko,et al.  The Vietnam Era Twin Registry , 2002, Twin Research.

[26]  Dorret I Boomsma,et al.  Genetic correlations between brain volumes and the WAIS-III dimensions of verbal comprehension, working memory, perceptual organization, and processing speed. , 2003, Twin research : the official journal of the International Society for Twin Studies.

[27]  Y. Sheline.  Neuroimaging studies of mood disorder effects on the brain , 2003, Biological Psychiatry.

[28]  I. Gottesman,et al.  The endophenotype concept in psychiatry: etymology and strategic intentions. , 2003, The American journal of psychiatry.

[29]  William B. Dobyns,et al.  G Protein-Coupled Receptor-Dependent Development of Human Frontal Cortex , 2004, Science.

[30]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[31]  Suzanne E. Welcome,et al.  Longitudinal Mapping of Cortical Thickness and Brain Growth in Normal Children , 2022 .

[32]  Konstantine K. Zakzanis,et al.  A Meta-Analysis of Structural and Functional Brain Imaging in Dementia of the Alzheimer's Type: A Neuroimaging Profile , 2003, Neuropsychology Review.

[33]  Terry L. Jernigan,et al.  Changes in volume with age—consistency and interpretation of observed effects , 2005, Neurobiology of Aging.

[34]  E. Andermann,et al.  Genetics of the polymicrogyria syndromes , 2005, Journal of Medical Genetics.

[35]  Anders M. Dale,et al.  Cortical volume and speed-of-processing are complementary in prediction of performance intelligence , 2005, Neuropsychologia.

[36]  Cheryl L. Dahle,et al.  Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. , 2005, Cerebral cortex.

[37]  Alan C. Evans,et al.  Genetic Contributions to Human Brain Morphology and Intelligence , 2006, The Journal of Neuroscience.

[38]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[39]  Corwin Boake,et al.  Genes, Environment, and Time: The Vietnam Era Twin Study of Aging (VETSA) , 2006, Twin Research and Human Genetics.

[40]  P. Thompson,et al.  Neuroimaging endophenotypes: Strategies for finding genes influencing brain structure and function , 2007, Human brain mapping.

[41]  R. Kahn,et al.  Genetic influences on human brain structure: A review of brain imaging studies in twins , 2007, Human brain mapping.

[42]  Robert F. Hevner,et al.  Role of Intermediate Progenitor Cells in Cerebral Cortex Development , 2007, Developmental Neuroscience.

[43]  Kelly Rehm,et al.  Regionally specific cortical thinning and gray matter abnormalities in the healthy relatives of schizophrenia patients. , 2006, Cerebral cortex.

[44]  Michael I. Miller,et al.  Abnormalities of cingulate gyrus neuroanatomy in schizophrenia , 2007, Schizophrenia Research.

[45]  J. Giedd,et al.  Review of Twin and Family Studies on Neuroanatomic Phenotypes and Typical Neurodevelopment , 2007, Twin Research and Human Genetics.

[46]  Pasko Rakic,et al.  The radial edifice of cortical architecture: From neuronal silhouettes to genetic engineering , 2007, Brain Research Reviews.

[47]  Alan C. Evans,et al.  Brain size and cortical structure in the adult human brain. , 2008, Cerebral cortex.

[48]  E. Bullmore,et al.  The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. , 2008, The American journal of psychiatry.

[49]  J. Lagopoulos,et al.  Anatomical abnormalities of the anterior cingulate and paracingulate cortex in patients with bipolar I disorder , 2008, Psychiatry Research: Neuroimaging.

[50]  M. Keshavan,et al.  Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic‐naïve schizophrenia , 2008, Acta psychiatrica Scandinavica.

[51]  N. Kabani,et al.  Identification of genetically mediated cortical networks: a multivariate study of pediatric twins and siblings. , 2008, Cerebral cortex.

[52]  J. Morris,et al.  Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area , 2009, Neurobiology of Aging.

[53]  Alan C. Evans,et al.  Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence , 2009, Human brain mapping.