Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment
Previous studies have suggested that altered asymmetry of the planum temporale (PT) is associated with neurodevelopmental disorders, including dyslexia, schizophrenia, and autism. Shared genetic factors have been suggested to link PT asymmetry to these disorders. In a dataset of unrelated subjects f...
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| Published in | Cortex Vol. 124; pp. 137 - 153 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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Elsevier Ltd
01.03.2020
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| Abstract | Previous studies have suggested that altered asymmetry of the planum temporale (PT) is associated with neurodevelopmental disorders, including dyslexia, schizophrenia, and autism. Shared genetic factors have been suggested to link PT asymmetry to these disorders. In a dataset of unrelated subjects from the general population (UK Biobank, N = 18,057), we found that PT volume asymmetry had a significant heritability of roughly 14%. In genome-wide association analysis, two loci were significantly associated with PT asymmetry, including a coding polymorphism within the gene ITIH5 that is predicted to affect the protein's function and to be deleterious (rs41298373, p = 2.01 × 10–15), and a locus that affects the expression of the genes BOK and DTYMK (rs7420166, p = 7.54 × 10-10). DTYMK showed left-right asymmetry of mRNA expression in post mortem PT tissue. Cortex-wide mapping of these SNP effects revealed influences on asymmetry that went somewhat beyond the PT. Using publicly available genome-wide association statistics from large-scale studies, we saw no significant genetic correlations of PT asymmetry with autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, educational attainment or intelligence. Of the top two individual loci associated with PT asymmetry, rs41298373 showed a tentative association with intelligence (unadjusted p = .025), while the locus at BOK/DTYMK showed tentative association with educational attainment (unadjusted Ps < .05). These findings provide novel insights into the genetic contributions to human brain asymmetry, but do not support a substantial polygenic association of PT asymmetry with cognitive variation and mental disorders, as far as can be discerned with current sample sizes. |
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| AbstractList | Previous studies have suggested that altered asymmetry of the planum temporale (PT) is associated with neurodevelopmental disorders, including dyslexia, schizophrenia, and autism. Shared genetic factors have been suggested to link PT asymmetry to these disorders. In a dataset of unrelated subjects from the general population (UK Biobank, N = 18,057), we found that PT volume asymmetry had a significant heritability of roughly 14%. In genome-wide association analysis, two loci were significantly associated with PT asymmetry, including a coding polymorphism within the gene ITIH5 that is predicted to affect the protein's function and to be deleterious (rs41298373, p = 2.01 × 10-15), and a locus that affects the expression of the genes BOK and DTYMK (rs7420166, p = 7.54 × 10-10). DTYMK showed left-right asymmetry of mRNA expression in post mortem PT tissue. Cortex-wide mapping of these SNP effects revealed influences on asymmetry that went somewhat beyond the PT. Using publicly available genome-wide association statistics from large-scale studies, we saw no significant genetic correlations of PT asymmetry with autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, educational attainment or intelligence. Of the top two individual loci associated with PT asymmetry, rs41298373 showed a tentative association with intelligence (unadjusted p = .025), while the locus at BOK/DTYMK showed tentative association with educational attainment (unadjusted Ps < .05). These findings provide novel insights into the genetic contributions to human brain asymmetry, but do not support a substantial polygenic association of PT asymmetry with cognitive variation and mental disorders, as far as can be discerned with current sample sizes. Previous studies have suggested that altered asymmetry of the planum temporale (PT) is associated with neurodevelopmental disorders, including dyslexia, schizophrenia, and autism. Shared genetic factors have been suggested to link PT asymmetry to these disorders. In a dataset of unrelated subjects from the general population (UK Biobank, N = 18,057), we found that PT volume asymmetry had a significant heritability of roughly 14%. In genome-wide association analysis, two loci were significantly associated with PT asymmetry, including a coding polymorphism within the gene ITIH5 that is predicted to affect the protein's function and to be deleterious (rs41298373, p = 2.01 × 10-15), and a locus that affects the expression of the genes BOK and DTYMK (rs7420166, p = 7.54 × 10-10). DTYMK showed left-right asymmetry of mRNA expression in post mortem PT tissue. Cortex-wide mapping of these SNP effects revealed influences on asymmetry that went somewhat beyond the PT. Using publicly available genome-wide association statistics from large-scale studies, we saw no significant genetic correlations of PT asymmetry with autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, educational attainment or intelligence. Of the top two individual loci associated with PT asymmetry, rs41298373 showed a tentative association with intelligence (unadjusted p = .025), while the locus at BOK/DTYMK showed tentative association with educational attainment (unadjusted Ps < .05). These findings provide novel insights into the genetic contributions to human brain asymmetry, but do not support a substantial polygenic association of PT asymmetry with cognitive variation and mental disorders, as far as can be discerned with current sample sizes.Previous studies have suggested that altered asymmetry of the planum temporale (PT) is associated with neurodevelopmental disorders, including dyslexia, schizophrenia, and autism. Shared genetic factors have been suggested to link PT asymmetry to these disorders. In a dataset of unrelated subjects from the general population (UK Biobank, N = 18,057), we found that PT volume asymmetry had a significant heritability of roughly 14%. In genome-wide association analysis, two loci were significantly associated with PT asymmetry, including a coding polymorphism within the gene ITIH5 that is predicted to affect the protein's function and to be deleterious (rs41298373, p = 2.01 × 10-15), and a locus that affects the expression of the genes BOK and DTYMK (rs7420166, p = 7.54 × 10-10). DTYMK showed left-right asymmetry of mRNA expression in post mortem PT tissue. Cortex-wide mapping of these SNP effects revealed influences on asymmetry that went somewhat beyond the PT. Using publicly available genome-wide association statistics from large-scale studies, we saw no significant genetic correlations of PT asymmetry with autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, educational attainment or intelligence. Of the top two individual loci associated with PT asymmetry, rs41298373 showed a tentative association with intelligence (unadjusted p = .025), while the locus at BOK/DTYMK showed tentative association with educational attainment (unadjusted Ps < .05). These findings provide novel insights into the genetic contributions to human brain asymmetry, but do not support a substantial polygenic association of PT asymmetry with cognitive variation and mental disorders, as far as can be discerned with current sample sizes. |
| Author | Francks, Clyde Mazoyer, Bernard Crivello, Fabrice Tzourio-Mazoyer, Nathalie Kong, Xiang-Zhen Carrion-Castillo, Amaia Pepe, Antonietta Fisher, Simon E. |
| Author_xml | – sequence: 1 givenname: Amaia orcidid: 0000-0003-0226-0642 surname: Carrion-Castillo fullname: Carrion-Castillo, Amaia organization: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands – sequence: 2 givenname: Antonietta surname: Pepe fullname: Pepe, Antonietta organization: Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique, Commissariat à l’Energie Atomique, et Université; de Bordeaux, Bordeaux, France – sequence: 3 givenname: Xiang-Zhen surname: Kong fullname: Kong, Xiang-Zhen organization: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands – sequence: 4 givenname: Simon E. surname: Fisher fullname: Fisher, Simon E. organization: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands – sequence: 5 givenname: Bernard surname: Mazoyer fullname: Mazoyer, Bernard organization: Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique, Commissariat à l’Energie Atomique, et Université; de Bordeaux, Bordeaux, France – sequence: 6 givenname: Nathalie surname: Tzourio-Mazoyer fullname: Tzourio-Mazoyer, Nathalie organization: Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique, Commissariat à l’Energie Atomique, et Université; de Bordeaux, Bordeaux, France – sequence: 7 givenname: Fabrice orcidid: 0000-0001-6950-984X surname: Crivello fullname: Crivello, Fabrice organization: Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique, Commissariat à l’Energie Atomique, et Université; de Bordeaux, Bordeaux, France – sequence: 8 givenname: Clyde orcidid: 0000-0002-9098-890X surname: Francks fullname: Francks, Clyde email: clyde.francks@mpi.nl organization: Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31887566$$D View this record in MEDLINE/PubMed |
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| Keywords | Genetic correlation Brain asymmetry UK biobank Genome-wide association Neurodevelopmental disorders Planum temporale |
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| SubjectTerms | Autism Spectrum Disorder - genetics Brain asymmetry Functional Laterality Genetic correlation Genome-wide association Genome-Wide Association Study Humans Intelligence - genetics Magnetic Resonance Imaging Neurodevelopmental disorders Nucleoside-Phosphate Kinase - genetics Planum temporale Proteinase Inhibitory Proteins, Secretory - genetics Proto-Oncogene Proteins c-bcl-2 - genetics Temporal Lobe UK biobank |
| Title | Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment |
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