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Questions {❓}

• Liu YJ, Papasian CJ, Liu JF, Hamilton J, Deng HW (2008) Is replication the gold standard for validating genome-wide association findings?
• Spencer JPE (2008) Flavonoids: modulators of brain function?

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         headline:Genetics of structural connectivity and information processing in the brain
         description: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.
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      headline:Genetics of structural connectivity and information processing in the brain
      description: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.
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         Imaging genetics
         DTI
         GWAS
         Processing speed
         Fractional anisotropy
         Cognition
         Neurosciences
         Cell Biology
         Neurology
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      affiliation:
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            address:
               name:Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden
               type:PostalAddress
            type:Organization
            name:Umeå University
            address:
               name:Department of Radiation Sciences, Umeå University, Umeå, Sweden
               type:PostalAddress
            type:Organization
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            address:
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               type:PostalAddress
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      email:[email protected]
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      name:Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
      name:K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway
      name:K.G. Jebsen Center for Psychosis Research, Norwegian Center for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
      name:Department of Psychology, University of Oslo, Oslo, Norway
      name:Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden
      name:Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden
      name:K.G. Jebsen Center for Psychosis Research, Norwegian Center for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
      name:Department of Psychology, University of Oslo, Oslo, Norway
      name:Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden
      name:Department of Statistics, USBF, Umeå University, Umeå, Sweden
      name:Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
      name:K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway
      name:Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland
      name:Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany
      name:Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
      name:Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden
      name:Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
      name:K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway
      name:Department of Psychology, University of Oslo, Oslo, Norway
      name:Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden
      name:ARC, Karolinska Institutet, Stockholm, Sweden
      name:Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
      name:K.G.Jebsen Center for Psychosis Research and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway
      name:Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden
      name:Department of Radiation Sciences, Umeå University, Umeå, Sweden
      name:Department of Integrative Medical Biology, Umeå University, Umeå, Sweden

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