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Cerebral Cortex Advance Access published March 18 2009 Cerebral Cortex doi 10 1093 cercor bhp026 Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness Matthew S Panizzon1 Christine Fennema Notestine1 2 Lisa T Eyler1 3 Terry L Jernigan1 2 Elizabeth Prom Wormley4 Michael Neale4 Kristen Jacobson5 Michael J Lyons6 Michael D Grant6 Carol E Franz1 Hong Xian7 Ming Tsuang1 8 9 Bruce Fischl10 Larry Seidman11 Anders Dale1 12 and William S Kremen1 3 8 1 Department of Psychiatry 2Department of Radiology University of California San Diego La Jolla CA 92093 USA 3San Diego Veterans Administration Health Care System San Diego CA 92161 USA 4Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University School of Medicine Richmond VA 23219 USA 5Department of Psychiatry University of Chicago Chicago IL 60637 USA 6 Department of Psychology Boston University Boston MA 02215 USA 7Department of Psychiatry Washington University School of Medicine St Louis MO 63130 USA 8Center for Behavioral Genomics University of California San Diego La Jolla CA 92093 USA 9Harvard Institute of Psychiatric Epidemiology and Genetics Harvard Medical School and School of Public Health Boston MA 02115 USA 10Department of Radiology Massachusetts General Hospital Boston MA 02129 USA 11Department of Psychiatry Harvard Medical School Boston MA 02115 USA and 12Department of Neurosciences University of California San Diego La Jolla CA 92093 USA 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 5 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 Keywords cortical volume genetic correlation heritability magnetic resonance imaging twin study Introduction Over the past decade the eld of neuroimaging has made extraordinary advances leading to increased precision in how the living brain can be

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