Megan L Campbell, Shareefa Dalvie, Alexey Shadrin, Dennis van der Meer, Kevin O'Connell, Oleksander Frei, Ole A Andreassen, Dan J Stein, Jaroslav Rokicki
{"title":"胼胝体亚区的分布遗传效应表明与神经精神障碍和相关特征有关。","authors":"Megan L Campbell, Shareefa Dalvie, Alexey Shadrin, Dennis van der Meer, Kevin O'Connell, Oleksander Frei, Ole A Andreassen, Dan J Stein, Jaroslav Rokicki","doi":"10.1017/neu.2023.32","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.</p><p><strong>Methods: </strong>We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.</p><p><strong>Results: </strong>We identified 70 independent loci with distributed effects across the five subregions of the CC (<i>p</i> < 5 × 10<sup>-8</sup>). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (<i>p</i> < 2.6 × 10<sup>-6</sup>). LDSC estimated the heritability of CC to (<i>h</i><sup>2</sup><sub>SNP</sub> = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, <i>r<sub>g</sub></i> = -0.09, SE = 0.03; <i>p</i> = 5.9 × 10<sup>-3</sup>) and drinks consumed per week (<i>r<sub>g</sub></i> = -0.09, SE = 0.02; <i>p</i> = 4.8 × 10<sup>-4</sup>), and volume of the mid-anterior subregion with BD (<i>r<sub>g</sub></i> = -0.12, SE = 0.02; <i>p</i> = 2.5 × 10<sup>-4</sup>), major depressive disorder (MDD) (<i>r<sub>g</sub></i> = -0.12, SE = 0.04; <i>p</i> = 3.6 × 10<sup>-3</sup>), drinks consumed per week (<i>r<sub>g</sub></i> = -0.13, SE = 0.04; <i>p</i> = 1.8 × 10<sup>-3</sup>) and cannabis use (<i>r<sub>g</sub></i> = -0.09, SE = 0.03; <i>p</i> = 8.4 × 10<sup>-3</sup>).</p><p><strong>Conclusions: </strong>Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"1-8"},"PeriodicalIF":3.8000,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891296/pdf/","citationCount":"0","resultStr":"{\"title\":\"Distributed genetic effects of the corpus callosum subregions suggest links to neuropsychiatric disorders and related traits.\",\"authors\":\"Megan L Campbell, Shareefa Dalvie, Alexey Shadrin, Dennis van der Meer, Kevin O'Connell, Oleksander Frei, Ole A Andreassen, Dan J Stein, Jaroslav Rokicki\",\"doi\":\"10.1017/neu.2023.32\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.</p><p><strong>Methods: </strong>We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.</p><p><strong>Results: </strong>We identified 70 independent loci with distributed effects across the five subregions of the CC (<i>p</i> < 5 × 10<sup>-8</sup>). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (<i>p</i> < 2.6 × 10<sup>-6</sup>). LDSC estimated the heritability of CC to (<i>h</i><sup>2</sup><sub>SNP</sub> = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, <i>r<sub>g</sub></i> = -0.09, SE = 0.03; <i>p</i> = 5.9 × 10<sup>-3</sup>) and drinks consumed per week (<i>r<sub>g</sub></i> = -0.09, SE = 0.02; <i>p</i> = 4.8 × 10<sup>-4</sup>), and volume of the mid-anterior subregion with BD (<i>r<sub>g</sub></i> = -0.12, SE = 0.02; <i>p</i> = 2.5 × 10<sup>-4</sup>), major depressive disorder (MDD) (<i>r<sub>g</sub></i> = -0.12, SE = 0.04; <i>p</i> = 3.6 × 10<sup>-3</sup>), drinks consumed per week (<i>r<sub>g</sub></i> = -0.13, SE = 0.04; <i>p</i> = 1.8 × 10<sup>-3</sup>) and cannabis use (<i>r<sub>g</sub></i> = -0.09, SE = 0.03; <i>p</i> = 8.4 × 10<sup>-3</sup>).</p><p><strong>Conclusions: </strong>Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.</p>\",\"PeriodicalId\":7066,\"journal\":{\"name\":\"Acta Neuropsychiatrica\",\"volume\":\" \",\"pages\":\"1-8\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2023-08-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891296/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Neuropsychiatrica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1017/neu.2023.32\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Neuropsychiatrica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/neu.2023.32","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
Distributed genetic effects of the corpus callosum subregions suggest links to neuropsychiatric disorders and related traits.
Background: The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.
Methods: We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.
Results: We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 × 10-8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 × 10-6). LDSC estimated the heritability of CC to (h2SNP = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg = -0.09, SE = 0.03; p = 5.9 × 10-3) and drinks consumed per week (rg = -0.09, SE = 0.02; p = 4.8 × 10-4), and volume of the mid-anterior subregion with BD (rg = -0.12, SE = 0.02; p = 2.5 × 10-4), major depressive disorder (MDD) (rg = -0.12, SE = 0.04; p = 3.6 × 10-3), drinks consumed per week (rg = -0.13, SE = 0.04; p = 1.8 × 10-3) and cannabis use (rg = -0.09, SE = 0.03; p = 8.4 × 10-3).
Conclusions: Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.
期刊介绍:
Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.