Ronald A Yeo1, Steven W Gangestad2, Esther Walton3, Stefan Ehrlich4, Jessica Pommy2, Jessica A Turner5, Jingyu Liu6, Andrew R Mayer7, S Charles Schulz8, Beng-Choon Ho9, Juan R Bustillo10, Thomas H Wassink9, Scott R Sponheim11, Eric M Morrow12, Vince D Calhoun6. 1. Department of Psychology, University of New Mexico, Albuquerque, NM, USA; The Mind Research Network, Albuquerque, NM, USA. Electronic address: ryeo@unm.edu. 2. Department of Psychology, University of New Mexico, Albuquerque, NM, USA. 3. MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden, Germany; Dresden University of Technology, Dresden, Germany. 4. MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden, Germany; Dresden University of Technology, Dresden, Germany; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. 5. The Mind Research Network, Albuquerque, NM, USA; Dept. of Psychology, Georgia State University, Atlanta, GA, USA; Neuroscience Institute, Georgia State University, Atlanta, GA, USA. 6. The Mind Research Network, Albuquerque, NM, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA. 7. The Mind Research Network, Albuquerque, NM, USA. 8. Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA. 9. Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. 10. The Mind Research Network, Albuquerque, NM, USA; Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA. 11. Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA; Minneapolis Veterans Administration Health Care System, Minneapolis, MN, USA. 12. Department of Molecular Biology, Cell Biology and Biochemistry, Laboratory for Molecular Medicine, Brown University, Providence, RI, USA.
Abstract
BACKGROUND: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. METHODS: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA). RESULTS: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes. LIMITATIONS: Though adequately powered, our sample size is small for a genetic study. CONCLUSIONS: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.
BACKGROUND: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. METHODS: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA). RESULTS: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes. LIMITATIONS: Though adequately powered, our sample size is small for a genetic study. CONCLUSIONS: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.
Authors: S R Sponheim; R E Jung; L J Seidman; R I Mesholam-Gately; D S Manoach; D S O'Leary; B C Ho; N C Andreasen; J Lauriello; S C Schulz Journal: J Psychiatr Res Date: 2009-10-29 Impact factor: 4.791
Authors: Esther Walton; Jessica Turner; Randy L Gollub; Dara S Manoach; Anastasia Yendiki; Beng-Choon Ho; Scott R Sponheim; Vince D Calhoun; Stefan Ehrlich Journal: Schizophr Bull Date: 2012-01-20 Impact factor: 9.306
Authors: R A Yeo; D Martinez; J Pommy; S Ehrlich; S C Schulz; B-C Ho; J R Bustillo; V D Calhoun Journal: Psychol Med Date: 2013-07-19 Impact factor: 7.723
Authors: Randy L Gollub; Jody M Shoemaker; Margaret D King; Tonya White; Stefan Ehrlich; Scott R Sponheim; Vincent P Clark; Jessica A Turner; Bryon A Mueller; Vince Magnotta; Daniel O'Leary; Beng C Ho; Stefan Brauns; Dara S Manoach; Larry Seidman; Juan R Bustillo; John Lauriello; Jeremy Bockholt; Kelvin O Lim; Bruce R Rosen; S Charles Schulz; Vince D Calhoun; Nancy C Andreasen Journal: Neuroinformatics Date: 2013-07
Authors: Gabriëlla A M Blokland; Raquelle I Mesholam-Gately; Timothea Toulopoulou; Elisabetta C Del Re; Max Lam; Lynn E DeLisi; Gary Donohoe; James T R Walters; Larry J Seidman; Tracey L Petryshen Journal: Schizophr Bull Date: 2017-07-01 Impact factor: 9.306
Authors: Gabriëlla A M Blokland; Elisabetta C Del Re; Raquelle I Mesholam-Gately; Jorge Jovicich; Joey W Trampush; Matcheri S Keshavan; Lynn E DeLisi; James T R Walters; Jessica A Turner; Anil K Malhotra; Todd Lencz; Martha E Shenton; Aristotle N Voineskos; Dan Rujescu; Ina Giegling; René S Kahn; Joshua L Roffman; Daphne J Holt; Stefan Ehrlich; Zora Kikinis; Paola Dazzan; Robin M Murray; Marta Di Forti; Jimmy Lee; Kang Sim; Max Lam; Rick P F Wolthusen; Sonja M C de Zwarte; Esther Walton; Donna Cosgrove; Sinead Kelly; Nasim Maleki; Lisa Osiecki; Marco M Picchioni; Elvira Bramon; Manuela Russo; Anthony S David; Valeria Mondelli; Antje A T S Reinders; M Aurora Falcone; Annette M Hartmann; Bettina Konte; Derek W Morris; Michael Gill; Aiden P Corvin; Wiepke Cahn; New Fei Ho; Jian Jun Liu; Richard S E Keefe; Randy L Gollub; Dara S Manoach; Vince D Calhoun; S Charles Schulz; Scott R Sponheim; Donald C Goff; Stephen L Buka; Sara Cherkerzian; Heidi W Thermenos; Marek Kubicki; Paul G Nestor; Erin W Dickie; Evangelos Vassos; Simone Ciufolini; Tiago Reis Marques; Nicolas A Crossley; Shaun M Purcell; Jordan W Smoller; Neeltje E M van Haren; Timothea Toulopoulou; Gary Donohoe; Jill M Goldstein; Larry J Seidman; Robert W McCarley; Tracey L Petryshen Journal: Schizophr Res Date: 2017-10-03 Impact factor: 4.939