Common genetic variants shared among five major psychiatric disorders: a large-scale genome-wide combined analysis

Lu, Xia; Xia, Kun; Weinberger, Daniel R.; Zhang, Fengyu

doi:10.36316/gcatr.01.0003

Cited by 13 publications

(14 citation statements)

References 35 publications

(32 reference statements)

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“…In an attempt to replicate the variants identified in the recent large-scale genome-wide meta-analyses of five neuropsychiatric disorders in European ancestry [Xia et al, 2019], we only found that 35 SNPs associated with SCZ at genomewide significance were consistently replicated in our combined two cohorts of autism triad samples at a nominal level (P < 0.05). Unfortunately, we did not find consistent replication for SNPs that have been associated with other neuropsychiatric disorders, including bipolar, MDD, and ADHD, at genome-wide significance.…”

Section: Genementioning

confidence: 80%

“…Of these 15 SNPs, six were cis ‐eQTLs, including ERICH1 in the anterior cingulate cortex of the human brain. However, we noted that rs34458570, rs35012775, rs4735931, and rs4735932 at ERICH1‐AS1 had been identified at genome‐wide significance by a combined analysis of ADHD and ASD for shared genetic variants for childhood‐onset disorders [Xia et al, ]. The SNP rs4496877 had strong cis ‐association with KCNH2 in the cerebellum tissue of the GTEx data set; it is in LD ( D ′ = 1) with rs3800779, rs748693, and rs1036145 at KCNH2 in both Asian and European ancestry samples of the 1,000 Genomes.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple novel loci were implicated as strong signals for associations with autism, and most of them have been reported in the GWAS of other neuropsychiatric disorders. Our study provides insights into the genetic etiology of autism and common genetic variants shared across neuropsychiatric disorders, including SCZ, ASD, bipolar disorder, major depressive disorder (MDD) [Grove et al, 2019;Xia, Xia, Weinberger, & Zhang, 2019] and attention-deficit/hyperactivity disorder (ADHD) [Stergiakouli et al, 2017].…”

Section: Introductionmentioning

confidence: 99%

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Genome‐wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders

et al. 2019

Autism Research

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Autism is a common neurodevelopmental disorder with a moderate to a high degree of heritability, but only a few common genetic variants that explain the heritability have been associated. We performed a genome‐wide transmission disequilibrium test analysis of a newly genotyped autism case–parent triad samples (127 trios) in Han Chinese, identified top association signals at multiple single nucleotide polymorphisms (SNPs), including rs9839376 (OR = 2.59, P = 1.27 × 10−05) at KCNMB2, rs6044680 (OR = 0.319, P = 4.82 × 10−05) and rs7274133 (OR = 0.313, P = 3.22 × 10−05) at PCSK2, and rs310619 (OR = 2.40, P = 7.44 × 10−05) at EEF1A2. Furthermore, a genome‐wide combined P‐value of individual SNPs in two independent case–parent triad samples (total 402 triads, n = 1,206) identified SNPs at EGFLAM, ZDHHC2, AGBL1, and SNX29 as additional association signals for autism. While none of these signals achieved a genome‐wide significance in the two samples of our study, they have been reported in a previous genome‐wide association study of neuropsychiatric disorders, and the majority of these SNP have a significant cis‐regulatory association with mRNA in human tissues (false discovery rate (FDR) < 0.05). Our study warrants further study or replication with additional sample for association with autism and other neuropsychiatric disorders. Autism Res 2020, 13: 382–396. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Autism is a common neurodevelopmental disorder, heritable, but only a few common genetic variants that explain the heritability have been associated. We conducted a genome‐wide association study with two cohorts of autism case–parent triad samples in Han Chinese and identified multiple single nucleotide polymorphisms that were reported as strong association signals in a previous genome‐wide association study of other neuropsychiatric disorders or related traits. Our study provides evidence for shared genetic variants among autism and other neuropsychiatric disorders.

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Section: Genementioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genome‐wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders

et al. 2019

Autism Research

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“…ZFP57, ZNF165, ZSCAN23, ZSCAN31, ZSCAN9). Previous studies have identified loci linked to phenotype-related SNPs and genes that they can disrupt 13,19,20 . For example, genetic variants at 3p21 region were linked to GLYCTK, GNL3 and ITIH4 genes that were previously implicated in BD and SCZ 21,22 .…”

Section: Psychiatric Disorders and Cognition Share Common Egenesmentioning

confidence: 99%

Decoding the multimorbidities among psychiatric disorders and cognitive functioning

Golovina

Vickers

Erb

et al. 2019

Preprint

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The regulatory contribution that single-nucleotide polymorphisms (SNPs) associated with psychiatric and cognitive phenotypes make to multimorbidity is unknown. Here, we integrate 3D genome organization and expression quantitative trait (eQTL) analyses to identify the genes and biological pathways that are functionally impacted by 2,893 GWAS SNPs associated with cognitive functioning and five psychiatric disorders (i.e. attention deficit hyperactivity disorder (ADHD), anxiety, bipolar disorder (BD), unipolar depression (UD) and schizophrenia (SCZ)). The analysis revealed 33 genes and 62 pathways that were commonly affected by the gene regulatory interactions associated with all six phenotypes despite there being no common SNPs and eQTLs. 38 ADHD-, 78 anxiety-, 81 BD-, 169 UD-, 225 SCZ-and 185 cognition-associated genes represent known drug targets. Four genes were affected by eQTLs from all six phenotypes. Collectively, our results represent the foundation for a shift from a gene-targeted towards a pathway-based approach to the treatment of multimorbid conditions.

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“…2019;4:e190010. https://doi.org/10.20900/jpbs.20190010 disorders indicate that common genetic variants shared between ADHD and ASD are mainly located at genomic regions with CNVs that have been associated with ASD [14].…”

Section: Introductionmentioning

confidence: 99%

ULK4 Genetic Variants Have Pleiotropic Effect on Risk of Autism, Associated with Brain mRNA Expression and Antipsychotic Treatment Response

2019

J Psychiatry Brain Sci

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Background: ULK4 genetic variants have been implicated for adult-onset psychiatric disorders, and common variants are associated with hematologic and cardiologic disorders at genome-wide significance. This study aimed to examine the pleiotropic effect of ULK4 on the risk of autism, cis-association with mRNA and impact on antipsychotic treatment response in humans. Methods: The clinical genetic data comprised one cohort of autism caseparent triad sample in the Han Chinese and three cohorts of family-based samples in the European ancestry, from Autism Genetic Research Exchange, the Autism Genome Project and the Simons Foundation for Autism Research Initiative; mRNA expression in postmortem human prefrontal cortex across the lifespan and different brain regions of postmortem human brain and other tissues from two independent datasets were used for examining the cis-association with ULK4 variants. Antipsychotic treatment response data were from the Clinical Antipsychotic Trials in Intervention Effectiveness in patients with chronic schizophrenia. Transmission disequilibrium test was used to examine the genetic association with autism. General linear regression analysis was

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Common genetic variants shared among five major psychiatric disorders: a large-scale genome-wide combined analysis

Cited by 13 publications

References 35 publications

Genome‐wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders

Genome‐wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders

Decoding the multimorbidities among psychiatric disorders and cognitive functioning

ULK4 Genetic Variants Have Pleiotropic Effect on Risk of Autism, Associated with Brain mRNA Expression and Antipsychotic Treatment Response

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