<i>FoxP2</i>is significantly associated with schizophrenia and major depression in the Chinese Han Population

Li, Tao; Zeng, Zhen; Zhao, Qian; Wang, Ti; Huang, Ke; Li, Junyan; Li, You; Liu, Jie; Wei, Zengxin; Wang, Yang; Gao, Feng; He, Lin; Shi, Yongyong

doi:10.3109/15622975.2011.615860

Cited by 39 publications

(22 citation statements)

References 28 publications

(35 reference statements)

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“…The fact that SCZ patients often show language impairments such as reading difficulties [42] renders FOXP2 a plausible SCZ candidate gene. Interestingly, a previous study reported an association between genetic variation in FOXP2 and SCZ in a Han Chinese population [43]. Furthermore, Walker et al [44] identified FOXP2 as an inhibitor of the promoter activity and protein expression of DISC1 .…”

Section: Discussionmentioning

confidence: 99%

Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

et al. 2014

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In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional consequences of such single-nucleotide polymorphisms (SNPs) in the affected genes or their regulatory regions. The Global Test was applied to detect schizophrenia-associated pathways using discovery and replication datasets comprising 5,040 and 5,082 individuals of European ancestry, respectively. Information concerning functional gene-sets was retrieved from the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and the Molecular Signatures Database. Fourteen of the gene-sets or pathways identified in the discovery dataset were confirmed in the replication dataset. These include functional processes involved in transcriptional regulation and gene expression, synapse organization, cell adhesion, and apoptosis. For two genes, i.e. CTCF and CACNB2, evidence for association with schizophrenia was available (at the gene-level) in both the discovery study and published data from the Psychiatric Genomics Consortium schizophrenia study. Furthermore, these genes mapped to four of the 14 presently identified pathways. Several of the SNPs assigned to CTCF and CACNB2 have potential functional consequences, and a gene in close proximity to CACNB2, i.e. ARL5B, was identified as a potential gene of interest. Application of the present hierarchical approach thus allowed: (1) identification of novel biological gene-sets or pathways with potential involvement in the etiology of schizophrenia, as well as replication of these findings in an independent cohort; (2) detection of genes of interest for future follow-up studies; and (3) the highlighting of novel genes in previously reported candidate regions for schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

et al. 2014

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“…Association of one SNP with attention deficit hyperactivity disorder (ADHD) held in only one of two cohorts tested and for only one subset of cases (131). A study of FOXP2 in >1,000 Chinese schizophrenia cases and the same number of controls reported an association for one of twelve SNPs tested (87). This variant was also associated with major depression, but not bipolar disorder.…”

Section: Making the Most Of High-throughput Technologiesmentioning

confidence: 96%

Understanding Language from a Genomic Perspective

2015

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Language is a defining characteristic of the human species, but its foundations remain mysterious. Heritable disorders offer a gateway into biological underpinnings, as illustrated by the discovery that FOXP2 disruptions cause a rare form of speech and language impairment. The genetic architecture underlying language-related disorders is complex, and although some progress has been made, it has proved challenging to pinpoint additional relevant genes with confidence. Next-generation sequencing and genome-wide association studies are revolutionizing understanding of the genetic bases of other neurodevelopmental disorders, like autism and schizophrenia, and providing fundamental insights into the molecular networks crucial for typical brain development. We discuss how a similar genomic perspective, brought to the investigation of language-related phenotypes, promises to yield equally informative discoveries. Moreover, we outline how follow-up studies of genetic findings using cellular systems and animal models can help to elucidate the biological mechanisms involved in the development of brain circuits supporting language.

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“…FAF1 (Fas Associated Factor 1) encodes a protein which binds the Fas antigen to initiate or facilitate apoptosis, amongst a wide range of other biological processes (including neuronal cell survival) (Menges, Altomare and Testa, 2009 (Giudicessi et al, 2011;Duarri et al, 2012;Lee et al, 2012), Systemic lupus erythematosus (SLE) (Y RNAs) (Kowalski and Krude, 2015), Joubert syndrome 31 and short-rib thoracic dysplasia 13 (CEP120) (Roosing et al, 2016), Amyotrophic lateral sclerosis (ALS) (FAF1) (Baron et al, 2014), Urbach-Wiethe disease (ECM1) (Hamada et al, 2003;Oyama et al, 2003), mental retardation and other cohesinopathies such as Cornelia de Lange Syndrome (STAG1) (Liu and Krantz, 2009;Lehalle et al, 2017), split hand/ split foot malformation (DYNC1I1) (Roberts et al, 1991;Tayebi et al, 2014), and a wide range of cancers (PRC1) (Li et al, 2018). Other disorders found to involve MCP-related genes include schizophrenia (FOXP2 and GABRB2) (Petryshen et al, 2005;Sanjuá et al, 2006;Lo et al, 2007;Laroche et al, 2008;Tolosa et al, 2010;Li et al, 2013;Yin et al, 2018), intellectual disability and epilepsy (GABRB2) (Srivastava et al, 2014), and neuroleptic-induced tardive dyskinesia (GABRB2) (Inada et al, 2008).…”

Section: Genes Of Interest Identified In Gwas Of Mcpmentioning

confidence: 99%

Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

Johnston

Adams

Nicholl

et al. 2018

Preprint

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Chronic pain is highly prevalent worldwide, contributing a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype, chronic pain grade, have been shown to be complex, heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested. We have here made use of a measure of the number of sites of chronic pain in individuals within the general UK population. This measure, termed Multisite Chronic Pain (MCP), is also a complex trait, but its genetic architecture has not previously been investigated. To address this, a large-scale genome-wide association study (GWAS) of MCP was carried out in ~380,000 UK Biobank participants to identify associated genetic variants. Findings were consistent with MCP having a significant polygenic component with a SNP heritability of 10.2%, and 76 independent lead single nucleotide polymorphisms (SNPs) at 39 risk loci were identified. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as being enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits including major depressive disorder (MDD), asthma and BMI. Furthermore, in Mendelian randomisation (MR) analyses a bi-directional causal relationship was observed between MCP and MDD. A polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. These findings support the proposition that chronic pain involves a strong nervous system component and have implications for our understanding of the physiology of chronic pain and for the development of novel treatment strategies.

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FoxP2is significantly associated with schizophrenia and major depression in the Chinese Han Population

Abstract: Our study indicated that the rare variant rs10447760 in FoxP2 may play an important role in schizophrenia and major depression in the Chinese Han population.

Cited by 39 publications

References 28 publications

Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

Understanding Language from a Genomic Perspective

Genome-wide Association Study of Multisite Chronic Pain in UK Biobank

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