Putative complement control protein CSMD3 dysfunction impairs synaptogenesis and induces neurodevelopmental disorders

Song, Wei; Quan, Li; Wang, Tao; Li, Yuanyuan; Fan, Tianda; Zhang, Jianghong; Wang, Qingqing; Pan, Jinrong; Dong, Qiwen; Sun, Zhong Sheng; Wang, Yan

doi:10.1016/j.bbi.2022.02.027

Cited by 18 publications

(10 citation statements)

References 73 publications

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“…Consistent with this hypothesis, 9 of 19 novel genes identified in our EUR MTAG analysis were significant in GWAS of depression or schizophrenia [41][42][43][44][45]. Furthermore, several of the novel genes (SYNGAP1, ZNF804A, CSMD3, DNM3, LRFN5, TCF20 and TNRC6B) have been previously associated with neurodevelopmental disorders [46][47][48][49][50][51][52]. Mutations in SYNGAP1 reduce protein activity, leading to impaired synaptic plasticity, a key factor in brain development [46].…”

Section: Discussionsupporting

confidence: 75%

“…Mutations in SYNGAP1 reduce protein activity, leading to impaired synaptic plasticity, a key factor in brain development [46]. Autism patients have lower expression of ZFN804A in the anterior cingulate gyrus [47], and CSMD4 has been identified as a risk gene for autism spectrum disorder [48]. Our results suggest a connection between SUTs and neurodevelopmental disorders.…”

Section: Discussionmentioning

confidence: 80%

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Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study

Toikumo

Crist

et al. 2023

Addiction

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Background and AimsGenome‐wide association studies (GWAS) of opioid use disorder (OUD) and cannabis use disorder (CUD) have lagged behind those of alcohol use disorder (AUD) and smoking, where many more loci have been identified. We sought to identify novel loci for substance use traits (SUTs) in both African‐ (AFR) and European‐ (EUR) ancestry individuals to enhance our understanding of the traits’ genetic architecture.DesignWe used multi‐trait analysis of GWAS (MTAG) to analyze four SUTs in EUR subjects (OUD, CUD, AUD and smoking initiation [SMKinitiation]), and three SUTs in AFR subjects (OUD, AUD and smoking trajectory [SMKtrajectory]). We conducted gene‐set and protein–protein interaction analyses and calculated polygenic risk scores (PRS) in two independent samples.SettingThis study was conducted in the United States.ParticipantsA total of 5692 EUR and 4918 AFR individuals in the Yale‐Penn sample and 29 054 EUR and 10 265 AFR individuals in the Penn Medicine BioBank sample.FindingsMTAG identified genome‐wide significant (GWS) single nucleotide polymorphisms (SNPs) for all four traits in EUR: 41 SNPs in 36 loci for OUD; 74 SNPs in 60 loci for CUD; 63 SNPs in 52 loci for AUD; and 183 SNPs in 144 loci for SMKinitiation. MTAG also identified GWS SNPs in AFR: 2 SNPs in 2 loci for OUD; 3 SNPs in 3 loci for AUD; and 1 SNP in 1 locus for SMKtrajectory. In the Yale‐Penn sample, the MTAG‐derived PRS consistently yielded more significant associations with both the corresponding substance use disorder diagnosis and multiple related phenotypes than the GWAS‐derived PRS.ConclusionsMulti‐trait analysis of genome‐wide association studies boosted the number of loci found for substance use traits, identifying genes not previously linked to any substance, and increased the power of polygenic risk scores. Multi‐trait analysis of genome‐wide association studies can be used to identify novel associations for substance use, especially those for which the samples are smaller than those for historically legal substances.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 80%

Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study

Toikumo

Crist

et al. 2023

Addiction

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“… 41 , 42 , 43 , 44 DNMs in coding regions reportedly contribute to ∼30% of all cases of simplex autism families and ∼45% of cases diagnosed in females. 44 We have identified several ASD genes 45 , 46 and demonstrated the contribution of DNMs to ASD aetiology in brain-size-related genes 47 and vitamin-related genes, 48 as well as revealed the convergence and divergence in DNMs among three ASD subcategories. 49 Furthermore, copy number variations (CNVs) contributed to the risk of developing ASD 50 , 51 , 52 , 53 and might account for ∼4% of ASD cases.…”

Section: Introductionmentioning

confidence: 86%

Integrative analysis prioritised oxytocin-related biomarkers associated with the aetiology of autism spectrum disorder

et al. 2022

Self Cite

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“…The top ve DEGs for each of the three pre-adipocyte clusters (Figure 2A) have established roles in cell development including cell-to-cell adhesion, proliferation and differentiation which have primarily been shown in synapse/neuronal cells [37][38][39][40][41][42][43][44][45][46][47][48][49] . It is therefore plausible that these novel genes play important yet understated roles in pre-adipocyte proliferation, commitment, and differentiation, particularly in humans.…”

Section: Pre-adipocytesmentioning

confidence: 99%

A single nuclei atlas of aging human abdominal subcutaneous white adipose tissue

Sparks

Whytock

Divoux

et al. 2023

Preprint

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White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell-specific transcriptional aberrations that occur in WAT with aging. We leveraged full-length snRNA-Seq to characterize the cellular landscape of human subcutaneous WAT in a prospective cohort of 10 Younger (≤ 30 years) and 10 Older individuals (≥ 65 years) balanced for sex and body mass index (BMI). We highlight that aging WAT is associated with adipocyte hypertrophy, increased proportions of resident macrophages (M2), an upregulated innate immune response and senescence profiles in specific adipocyte populations, highlighting CXCL14 as a biomarker of this process. We also identify novel markers of pre-adipocytes and track their expression levels through pre-adipocyte differentiation. We propose that aging WAT is associated with low-grade inflammation that is managed by a foundation of innate immunity to preserve the metabolic health of the WAT.

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Putative complement control protein CSMD3 dysfunction impairs synaptogenesis and induces neurodevelopmental disorders

Cited by 18 publications

References 73 publications

Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study

Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study

Integrative analysis prioritised oxytocin-related biomarkers associated with the aetiology of autism spectrum disorder

A single nuclei atlas of aging human abdominal subcutaneous white adipose tissue

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