Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.
- Authors
- Li, Zhiqiang; Chen, Jianhua; Yu, Hao; He, Lin; Xu, Yifeng; Zhang, Dai; Yi, Qizhong; Li, Changgui; Li, Xingwang; Shen, Jiawei; Song, Zhijian; Ji, Weidong; Wang, Meng; Zhou, Juan; Chen, Boyu; Liu, Yahui; Wang, Jiqiang; Wang, Peng; Yang, Ping; Wang, Qingzhong; Feng, Guoyin; Liu, Benxiu; Sun, Wensheng; Li, Baojie; He, Guang; Li, Weidong; Wan, Chunling; Xu, Qi; Li, Wenjin; Wen, Zujia; Liu, Ke; Huang, Fang; Ji, Jue; Ripke, Stephan; Yue, Weihua; Sullivan, Patrick F; O'Donovan, Michael C; Shi, Yongyong
- Year
- 2017
- Journal
- Nature genetics
- PMID
- 28991256
- DOI
- 10.1038/ng.3973
We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including โผ50% that achieved nominal significance and โผ75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.
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| C<sub>2</sub>H<sub>2</sub>-Type Zinc Finger Proteins in Brain Development, Neurodevelopmental, and Other Neuropsychiatric Disorders: Systematic Literature-Based Analysis. | Al-Naama N et al. | โ | 2020 | โ |
| CTLA4 mRNA expression in blood is lower in schizophrenia, but not in affective disorders. | Miyamoto K et al. | โ | 2020 | โ |
| Current challenges and possible future developments in personalized psychiatry with an emphasis on psychotic disorders. | Levchenko A et al. | โ | 2020 | โ |
| EEG microstates are a candidate endophenotype for schizophrenia. | da Cruz JR et al. | โ | 2020 | โ |
| Effect of ZNF804A gene polymorphism (rs1344706) on the plasticity of the functional coupling between the right dorsolateral prefrontal cortex and the contralateral hippocampal formation. | Zhao W et al. | โ | 2020 | โ |
| Enhancer Domains Predict Gene Pathogenicity and Inform Gene Discovery in Complex Disease. | Wang X et al. | โ | 2020 | โ |
| Epigenetic mechanism of SETDB1 in brain: implications for neuropsychiatric disorders. | Zhu Y et al. | โ | 2020 | โ |
| Evidence for altered energy metabolism, increased lactate, and decreased pH in schizophrenia brain: A focused review and meta-analysis of human postmortem and magnetic resonance spectroscopy studies. | Pruett BS et al. | โ | 2020 | โ |
| Exploring the Role of Contactins across Psychological, Psychiatric and Cardiometabolic Traits within UK Biobank. | Morris J et al. | โ | 2020 | โ |
| Fine-mapping of ZDHHC2 identifies risk variants for schizophrenia in the Han Chinese population. | Zhang H et al. | โ | 2020 | โ |
| Functional annotation of regulatory single nucleotide polymorphisms associated with schizophrenia. | Fahira A et al. | โ | 2020 | โ |
| Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data. | Li HJ et al. | โ | 2020 | โ |
| Genetic Intersections of Language and Neuropsychiatric Conditions. | Koomar T et al. | โ | 2020 | โ |
| Genome-wide Association Study of Creativity Reveals Genetic Overlap With Psychiatric Disorders, Risk Tolerance, and Risky Behaviors. | Li H et al. | โ | 2020 | โ |
| Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort. | Osborne AJ et al. | โ | 2020 | โ |
| Genome-Wide Scan for Five Brain Oscillatory Phenotypes Identifies a New QTL Associated with Theta EEG Band. | Rebelo Mร et al. | โ | 2020 | โ |
| Genome-Wide Search for SNP Interactions in GWAS Data: Algorithm, Feasibility, Replication Using Schizophrenia Datasets. | Lee KY et al. | โ | 2020 | โ |
| Genome-wide study of immune biomarkers in cerebrospinal fluid and serum from patients with bipolar disorder and controls. | Zhang R et al. | โ | 2020 | โ |
| Highly Recurrent Copy Number Variations in <i>GABRB2</i> Associated With Schizophrenia and Premenstrual Dysphoric Disorder. | Ullah A et al. | โ | 2020 | โ |
| Identification of a functional SNP rs7304782 at schizophrenia risk locus 12q24.31 and validation of its association with schiz ophrenia in Chinese populations. | Ma C et al. | โ | 2020 | โ |
| Identification of rare and common variants in BNIP3L: a schizophrenia susceptibility gene. | Zhou J et al. | โ | 2020 | โ |
| <i>MIR137</i> polygenic risk is associated with schizophrenia and affects functional connectivity of the dorsolateral prefrontal cortex. | Liu S et al. | โ | 2020 | โ |
| Impute.me: An Open-Source, Non-profit Tool for Using Data From Direct-to-Consumer Genetic Testing to Calculate and Interpret Polygenic Risk Scores. | Folkersen L et al. | โ | 2020 | โ |
| Integrated Analysis of Summary Statistics to Identify Pleiotropic Genes and Pathways for the Comorbidity of Schizophrenia and Cardiometabolic Disease. | Liu H et al. | โ | 2020 | โ |
| Investigation of Schizophrenia with Human Induced Pluripotent Stem Cells. | Powell SK et al. | โ | 2020 | โ |
| Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analyses. | Torrico B et al. | โ | 2020 | โ |
| Localizing Components of Shared Transethnic Genetic Architecture of Complex Traits from GWAS Summary Data. | Shi H et al. | โ | 2020 | โ |
| Long Noncoding RNA SOX2-OT: Regulations, Functions, and Roles on Mental Illnesses, Cancers, and Diabetic Complications. | Li PY et al. | โ | 2020 | โ |
| Long-term effects of stress early in life on microRNA-30a and its network: Preventive effects of lurasidone and potential implications for depression vulnerability. | Cattaneo A et al. | โ | 2020 | โ |
| Meta-analyses of genome wide association studies in lines of laying hens divergently selected for feather pecking using imputed sequence level genotypes. | Falker-Gieske C et al. | โ | 2020 | โ |
| Metabolic Dysregulation and Psychosocial Stress in Patients with Schizophrenia Spectrum Disorders: A Case-Control Study. | Misiak B et al. | โ | 2020 | โ |
| Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients. | Li M et al. | โ | 2020 | โ |
| Partitioning heritability analyses unveil the genetic architecture of human brain multidimensional functional connectivity patterns. | Feng J et al. | โ | 2020 | โ |
| Peripheral Blood Leukocyte RNA-Seq Identifies a Set of Genes Related to Abnormal Psychomotor Behavior Characteristics in Patients with Schizophrenia. | Zhang Y et al. | โ | 2020 | โ |
| Polygenic effects of schizophrenia on hippocampal grey matter volume and hippocampus-medial prefrontal cortex functional connectivity. | Liu S et al. | โ | 2020 | โ |
| Polygenic risk for autism spectrum disorder affects left amygdala activity and negative emotion in schizophrenia. | Qin Y et al. | โ | 2020 | โ |
| Polygenic Risk Scores for Subtyping of Schizophrenia. | Chen J et al. | โ | 2020 | โ |
| Polygenic risk scores in schizophrenia with clinically significant copy number variants. | Taniguchi S et al. | โ | 2020 | โ |
| Rare and common variants analysis of the EMB gene in patients with schizophrenia. | Zhou J et al. | โ | 2020 | โ |
| Rare variants and biological pathways identified in treatment-refractory depression. | McClain LL et al. | โ | 2020 | โ |
| Schizophrenia in a genomic era: a review from the pathogenesis, genetic and environmental etiology to diagnosis and treatment insights. | Zamanpoor M | โ | 2020 | โ |
| Searching Far and Genome-Wide: The Relevance of Association Studies in Amyotrophic Lateral Sclerosis. | Rich KA et al. | โ | 2020 | โ |
| Single-cell epigenomic analyses implicate candidate causal variants at inherited risk loci for Alzheimer's and Parkinson's diseases. | Corces MR et al. | โ | 2020 | โ |
| Solute Carrier Family 1 (<i>SLC1A1</i>) Contributes to Susceptibility and Psychopathology Symptoms of Schizophrenia in the Han Chinese Population. | Li W et al. | โ | 2020 | โ |
| SZDB2.0: an updated comprehensive resource for schizophrenia research. | Wu Y et al. | โ | 2020 | โ |
| The association between schizophrenia and the immune system: Review of the evidence from unbiased 'omic-studies'. | van Mierlo HC et al. | โ | 2020 | โ |
| The genetic basis for the inverse relationship between rheumatoid arthritis and schizophrenia. | Zamanpoor M et al. | โ | 2020 | โ |
| The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. | Coleman JRI et al. | โ | 2020 | โ |
| The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation. | Comer AL et al. | โ | 2020 | โ |
| The Malaria-High Blood Pressure Hypothesis: Revisited. | Nwokocha CR et al. | โ | 2020 | โ |
| The polygenic architecture of schizophrenia - rethinking pathogenesis and nosology. | Smeland OB et al. | โ | 2020 | โ |
| The Role of Zebrafish and Laboratory Rodents in Schizophrenia Research. | Langova V et al. | โ | 2020 | โ |
| Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes. | Etemadikhah M et al. | โ | 2020 | โ |
| Understanding the genetics of neuropsychiatric disorders: the potential role of genomic regulatory blocks. | Bareลกiฤ A et al. | โ | 2020 | โ |
| Wnt receptor gene <i>FZD1</i> was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort. | Liu X et al. | โ | 2020 | โ |
| A general statistic to test an optimally weighted combination of common and/or rare variants. | Zhang J et al. | โ | 2019 | โ |
| An Analysis of Cellular Communication Network Factor Proteins as Candidate Mediators of Postpartum Psychosis Risk. | Davies W | โ | 2019 | โ |
| Anxiogenic-like behavior and deficient attention/working memory in rats expressing the human DISC1 gene. | Wang AL et al. | โ | 2019 | โ |
| A Unique Genome-wide Association Study of a Psychiatric Disorder From India. | Nimgaonkar VL et al. | โ | 2019 | โ |
| Benefits and limitations of genome-wide association studies. | Tam V et al. | โ | 2019 | โ |
| Brain function, structure and genomic data are linked but show different sensitivity to duration of illness and disease stage in schizophrenia. | Luo N et al. | โ | 2019 | โ |
| Centromeric Satellite DNAs: Hidden Sequence Variation in the Human Population. | Miga KH | โ | 2019 | โ |
| Clinical use of current polygenic risk scores may exacerbate health disparities. | Martin AR et al. | โ | 2019 | โ |
| Comparative genetic architectures of schizophrenia in East Asian and European populations. | Lam M et al. | โ | 2019 | โ |
| Contribution of induced pluripotent stem cell technologies to the understanding of cellular phenotypes in schizophrenia. | Balan S et al. | โ | 2019 | โ |
| Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities. | Koromina M et al. | โ | 2019 | โ |
| DESE: estimating driver tissues by selective expression of genes associated with complex diseases or traits. | Jiang L et al. | โ | 2019 | โ |
| Evidence for cerebello-thalamo-cortical hyperconnectivity as a heritable trait for schizophrenia. | Cao H et al. | โ | 2019 | โ |
| From the neo-Kraepelinian framework to the new mechanical philosophy of psychiatry: regaining common sense | Joober R et al. | โ | 2019 | โ |
| Functional genomics reveal gene regulatory mechanisms underlying schizophrenia risk. | Huo Y et al. | โ | 2019 | โ |
| Gene pathogenicity prediction of Mendelian diseases via the random forest algorithm. | He S et al. | โ | 2019 | โ |
| Genes encoding SATB2-interacting proteins in adult cerebral cortex contribute to human cognitive ability. | Cera I et al. | โ | 2019 | โ |
| Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver. | รalฤฑลkan M et al. | โ | 2019 | โ |
| Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders. | Andrade A et al. | โ | 2019 | โ |
| Genetic Variants Associated With Anxiety and Stress-Related Disorders: A Genome-Wide Association Study and Mouse-Model Study. | Meier SM et al. | โ | 2019 | โ |
| Genome-wide association analysis of 19,629 individuals identifies variants influencing regional brain volumes and refines their genetic co-architecture with cognitive and mental health traits. | Zhao B et al. | โ | 2019 | โ |
| Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect. | Ikeda M et al. | โ | 2019 | โ |
| Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland. | Arnau-Soler A et al. | โ | 2019 | โ |
| Genomewide Study of Epigenetic Biomarkers of Opioid Dependence in European- American Women. | Montalvo-Ortiz JL et al. | โ | 2019 | โ |
| Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. | Grotzinger AD et al. | โ | 2019 | โ |
| Human-specific tandem repeat expansion and differential gene expression during primate evolution. | Sulovari A et al. | โ | 2019 | โ |
| Identification of the primate-specific gene BTN3A2 as an additional schizophrenia risk gene in the MHC loci. | Wu Y et al. | โ | 2019 | โ |
| <i>FOXP2</i> contributes to the cognitive impairment in chronic patients with schizophrenia. | Lang X et al. | โ | 2019 | โ |
| Improved detection of common variants in coronary artery disease and blood pressure using a pleiotropy cFDR method. | Mao XJ et al. | โ | 2019 | โ |
| Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania. | Malaria Genomic Epidemiology Network | โ | 2019 | โ |
| In-silico investigation of coding variants potentially affecting the functioning of the glutamatergic N-methyl-D-aspartate receptor in schizophrenia. | Tsavou A et al. | โ | 2019 | โ |
| Integration of methylation QTL and enhancer-target gene maps with schizophrenia GWAS summary results identifies novel genes. | Wu C et al. | โ | 2019 | โ |
| Investigating genetic links between grapheme-colour synaesthesia and neuropsychiatric traits. | Tilot AK et al. | โ | 2019 | โ |
| Mapping causal pathways from genetics to neuropsychiatric disorders using genome-wide imaging genetics: Current status and future directions. | Le BD et al. | โ | 2019 | โ |
| Microduplications at the 15q11.2 BP1-BP2 locus are enriched in patients with anorexia nervosa. | Chang X et al. | โ | 2019 | โ |
| Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda. | Stevenson A et al. | โ | 2019 | โ |
| Rare compound heterozygous missense <i>SPATA7</i> variations and risk of schizophrenia; whole-exome sequencing in a consanguineous family with affected siblings, follow-up sequencing and a case-control study. | Igeta H et al. | โ | 2019 | โ |
| Retrospective Association Analysis of Longitudinal Binary Traits Identifies Important Loci and Pathways in Cocaine Use. | Wu W et al. | โ | 2019 | โ |
| SLC39A8 is a risk factor for schizophrenia in Uygur Chinese: a case-control study. | Jian X et al. | โ | 2019 | โ |
| The Association Between Schizophrenia Risk Variants and Creativity in Healthy Han Chinese Subjects. | Wang D et al. | โ | 2019 | โ |
| The Drosophila Gene <i>Sulfateless</i> Modulates Autism-Like Behaviors. | Hope KA et al. | โ | 2019 | โ |
| Thinking About Schizophrenia in an Era of Genomic Medicine. | Weinberger DR | โ | 2019 | โ |
| Transcriptome association studies of neuropsychiatric traits in African Americans implicate <i>PRMT7</i> in schizophrenia. | Fiorica PN et al. | โ | 2019 | โ |
| Translational bioinformatics in mental health: open access data sources and computational biomarker discovery. | Tenenbaum JD et al. | โ | 2019 | โ |
| Use of the epigenetic toolboxโจto contextualize common variants associated with schizophrenia riskโฉ. | Rajarajan P et al. | โ | 2019 | โ |
| 3D genome and its disorganization in diseases. | Li R et al. | โ | 2018 | โ |
| A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family. | Glรถcklhofer CR et al. | โ | 2018 | โ |
| A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population. | Luo N et al. | โ | 2018 | โ |
| Association between cerebral dopamine neurotrophic factor (CDNF) 2 polymorphisms and schizophrenia susceptibility and symptoms in the Han Chinese population. | Yang Y et al. | โ | 2018 | โ |
| Combination of <i>G72</i> Genetic Variation and G72 Protein Level to Detect Schizophrenia: Machine Learning Approaches. | Lin E et al. | โ | 2018 | โ |
| Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes. | Yang CP et al. | โ | 2018 | โ |
| Estimating SNP-Based Heritability and Genetic Correlation in Case-Control Studies Directly and with Summary Statistics. | Weissbrod O et al. | โ | 2018 | โ |
| Further evidence for the genetic association between <i>CACNA1I</i> and schizophrenia. | Xie Y et al. | โ | 2018 | โ |
| Genetic and Epigenetic Alterations Underlie Oligodendroglia Susceptibility and White Matter Etiology in Psychiatric Disorders. | Chen X et al. | โ | 2018 | โ |
| Genetic architecture: the shape of the genetic contribution to human traits and disease. | Timpson NJ et al. | โ | 2018 | โ |
| Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations. | Yang Y et al. | โ | 2018 | โ |
| Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression. | Strawbridge RJ et al. | โ | 2018 | โ |
| Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese. | Zheng R et al. | โ | 2018 | โ |
| Glucose and Insulin-Related Traits, Type 2 Diabetes and Risk of Schizophrenia: A Mendelian Randomization Study. | Li Z et al. | โ | 2018 | โ |
| Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue. | Bhalala OG et al. | โ | 2018 | โ |
| Integration of Enhancer-Promoter Interactions with GWAS Summary Results Identifies Novel Schizophrenia-Associated Genes and Pathways. | Wu C et al. | โ | 2018 | โ |
| <i>VRK2</i>, a Candidate Gene for Psychiatric and Neurological Disorders. | Li M et al. | โ | 2018 | โ |
| Leveraging genome-wide association and clinical data in revealing schizophrenia subgroups. | Yin L et al. | โ | 2018 | โ |
| Meta-analysis of GABRB2 polymorphisms and the risk of schizophrenia combined with GWAS data of the Han Chinese population and psychiatric genomics consortium. | Zhang T et al. | โ | 2018 | โ |
| Mini-review: Update on the genetics of schizophrenia. | Coelewij L et al. | โ | 2018 | โ |
| Novel Translational Research Methodology and the Prospect to a Better Understanding of Neurodegenerative Disease. | Unschuld PG | โ | 2018 | โ |
| Recent Advances in the Genetics of Schizophrenia. | Avramopoulos D | โ | 2018 | โ |
| Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population. | Zhao L et al. | โ | 2018 | โ |
| Research Progress in Biological Studies of Schizophrenia in China in 2017. | Liu D et al. | โ | 2018 | โ |
| Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances. | Feng X et al. | โ | 2018 | โ |
| Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. | Davies G et al. | โ | 2018 | โ |
| The critical needs and challenges for genetic architecture studies in Africa. | Martin AR et al. | โ | 2018 | โ |
| The forty years of medical genetics in China. | Cai L et al. | โ | 2018 | โ |
| Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation. | Rhie SK et al. | โ | 2018 | โ |
| Using Full Genomic Information to Predict Disease: Breaking Down the Barriers Between Complex and Mendelian Diseases. | Jordan DM et al. | โ | 2018 | โ |
| Using mouse transgenic and human stem cell technologies to model genetic mutations associated with schizophrenia and autism. | St Clair D et al. | โ | 2018 | โ |
| Weighted Burden Analysis of Exome-Sequenced Case-Control Sample Implicates Synaptic Genes in Schizophrenia Aetiology. | Curtis D et al. | โ | 2018 | โ |
| Prospects for using risk scores in polygenic medicine. | Lewis CM et al. | โ | 2017 | โ |