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  Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment

Carrion Castillo, A., Pepe, A., Kong, X., Fisher, S. E., Mazoyer, B., Tzourio-Mazoyer, N., et al. (2020). Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment. Cortex, 124, 137-153. doi:10.1016/j.cortex.2019.11.006.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-4A7E-C Version Permalink: http://hdl.handle.net/21.11116/0000-0005-7277-5
Genre: Journal Article

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 Creators:
Carrion Castillo, Amaia1, Author              
Pepe, Antonietta2, Author
Kong, Xiangzhen1, Author              
Fisher, Simon E.1, 3, Author              
Mazoyer, Bernard2, Author
Tzourio-Mazoyer, Nathalie2, Author
Crivello, Fabrice2, Author
Francks, Clyde1, 3, 4, Author              
Affiliations:
1Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, Nijmegen, NL, ou_792549              
2Université de Bordeaux, Bordeaux, France, ou_persistent22              
3Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              
4Imaging Genomics, MPI for Psycholinguistics, Max Planck Society, ou_2579692              

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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=0.025), while the locus at BOK/DTYMK showed tentative association with educational attainment (unadjusted Ps<0.05). 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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Language(s): eng - English
 Dates: 2019-11-292020
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.cortex.2019.11.006
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Title: Cortex
  Other : Cortex
Source Genre: Journal
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Publ. Info: Milan [etc.] : Elsevier Masson SAS
Pages: - Volume / Issue: 124 Sequence Number: - Start / End Page: 137 - 153 Identifier: ISSN: 0010-9452
CoNE: https://pure.mpg.de/cone/journals/resource/954925393344