title: Genetics of structural connectivity and information processing in the brain.
abstract: Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10-08). Suggestive associations (Meta P value <1 × 10-06) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10-08). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10-07). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10-08), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10-07) and the multimodal analysis (Fisher P value = 1 × 10-07). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.
authors: Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021, Bergen, Norway.|K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, 5021, Bergen, Norway.
authors: Sudheer
authors: S
authors: Giddaluru
authors: K.G. Jebsen Center for Psychosis Research, Norwegian Center for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, 0424, Oslo, Norway.|Department of Psychology, University of Oslo, 0317, Oslo, Norway.
authors: Thomas
authors: T
authors: Espeseth
authors: Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187, Umeå, Sweden.|Aging Research Center, Karolinska Institutet and Stockholm University, 11330, Stockholm, Sweden.
authors: Alireza
authors: A
authors: Salami
authors: K.G. Jebsen Center for Psychosis Research, Norwegian Center for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, 0424, Oslo, Norway.|Department of Psychology, University of Oslo, 0317, Oslo, Norway.
authors: Lars T
authors: LT
authors: Westlye
authors: Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187, Umeå, Sweden.|Department of Statistics, USBF, Umeå University, 90187, Umeå, Sweden.
authors: Anders
authors: A
authors: Lundquist
authors: Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021, Bergen, Norway.|K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, 5021, Bergen, Norway.
authors: Andrea
authors: A
authors: Christoforou
authors: Division of Medical Genetics, Department of Biomedicine, University of Basel, 4058, Basel, Switzerland.|Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, 52425, Juelich, Germany.|Department of Genomics, Life and Brain Center, University of Bonn, 53127, Bonn, Germany.
authors: Sven
authors: S
authors: Cichon
authors: Department of Clinical Sciences, Psychiatry, Umeå University, 90187, Umeå, Sweden.
authors: Rolf
authors: R
authors: Adolfsson
authors: Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021, Bergen, Norway.|K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, 5021, Bergen, Norway.
authors: Vidar M
authors: VM
authors: Steen
authors: Department of Psychology, University of Oslo, 0317, Oslo, Norway.
authors: Ivar
authors: I
authors: Reinvang
authors: Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187, Umeå, Sweden.|ARC, Karolinska Institutet, Stockholm, Sweden.
authors: Lars Göran
authors: LG
authors: Nilsson
authors: Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021, Bergen, Norway.|K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, 5021, Bergen, Norway.
authors: Stéphanie
authors: S
authors: Le Hellard
authors: Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187, Umeå, Sweden. lars.nyberg@umu.se.|Department of Radiation Sciences, Umeå University, 90187, Umeå, Sweden. lars.nyberg@umu.se.|Department of Integrative Medical Biology, Umeå University, 90187, Umeå, Sweden. lars.nyberg@umu.se.
authors: Lars
authors: 0000-0002-3367-1746
authors: L
authors: Nyberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D066127:White Matter / Q000033:anatomy & histology* / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D004268:DNA-Binding Proteins; C108402:SCO-spondin; D014157:Transcription Factors; C117427:ZFPM2 protein, human
keywords: Cognition; DTI; Fractional anisotropy; GWAS; Imaging genetics; Processing speed