Genetics of structural connectivity and information processing in the brain

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...

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Main Authors:	Giddaluru, Sudheer, Espeseth, Thomas, Salami, Alireza, Westlye, Lars T., Lundquist, Anders, Christoforou, Andrea, Cichon, Sven, Adolfsson, Rolf, Steen, Vidar M., Reinvang, Ivar, Nilsson, Lars Göran, Le Hellard, Stéphanie, Nyberg, Lars
Format:	Online
Language:	English
Published:	Springer Berlin Heidelberg 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102980/

id	pubmed-5102980
recordtype	oai_dc
spelling	pubmed-51029802016-11-21 Genetics of structural connectivity and information processing in the brain Giddaluru, Sudheer Espeseth, Thomas Salami, Alireza Westlye, Lars T. Lundquist, Anders Christoforou, Andrea Cichon, Sven Adolfsson, Rolf Steen, Vidar M. Reinvang, Ivar Nilsson, Lars Göran Le Hellard, Stéphanie Nyberg, Lars Original Article 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. Springer Berlin Heidelberg 2016-02-06 2016 /pmc/articles/PMC5102980/ /pubmed/26852023 http://dx.doi.org/10.1007/s00429-016-1194-0 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Giddaluru, Sudheer Espeseth, Thomas Salami, Alireza Westlye, Lars T. Lundquist, Anders Christoforou, Andrea Cichon, Sven Adolfsson, Rolf Steen, Vidar M. Reinvang, Ivar Nilsson, Lars Göran Le Hellard, Stéphanie Nyberg, Lars
spellingShingle	Giddaluru, Sudheer Espeseth, Thomas Salami, Alireza Westlye, Lars T. Lundquist, Anders Christoforou, Andrea Cichon, Sven Adolfsson, Rolf Steen, Vidar M. Reinvang, Ivar Nilsson, Lars Göran Le Hellard, Stéphanie Nyberg, Lars Genetics of structural connectivity and information processing in the brain
author_facet	Giddaluru, Sudheer Espeseth, Thomas Salami, Alireza Westlye, Lars T. Lundquist, Anders Christoforou, Andrea Cichon, Sven Adolfsson, Rolf Steen, Vidar M. Reinvang, Ivar Nilsson, Lars Göran Le Hellard, Stéphanie Nyberg, Lars
author_sort	Giddaluru, Sudheer
title	Genetics of structural connectivity and information processing in the brain
title_short	Genetics of structural connectivity and information processing in the brain
title_full	Genetics of structural connectivity and information processing in the brain
title_fullStr	Genetics of structural connectivity and information processing in the brain
title_full_unstemmed	Genetics of structural connectivity and information processing in the brain
title_sort	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.
publisher	Springer Berlin Heidelberg
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102980/
_version_	1613720551458603008

Genetics of structural connectivity and information processing in the brain

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