Genetics of Schizophrenia and Bipolar Disorder

2017 ◽  
Author(s):  
Alexander Charney ◽  
Pamela Sklar
Keyword(s):  
Bipolar Disorder ◽  
Copy Number ◽  
Psychotic Disorders ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Common Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Number Variation

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.

Genetics of Schizophrenia and Bipolar Disorder

2013 ◽  
pp. 232-246 ◽  
Author(s):  
Pamela Sklar
Keyword(s):  
Bipolar Disorder ◽  
Copy Number ◽  
Psychotic Disorders ◽  
De Novo ◽  
Copy Number Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Sequencing Studies ◽  
Number Variation

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. The explosion of strong and convincing genetic evidence indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. There is a role for rare single nucleotide variation as well as de novo genetic variation being pointed to in new sequencing studies, but their overall contribution to risk is less clear. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, there is evidence for polygenicity and as yet no deep sequencing surveys have been published. Several intriguing biological pathways are suggested by these genetic findings related to microRNAs and calcium channel signaling. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder. Translating these results into biological and etiological understanding has not yet advanced, and will likely only do so when experimental methods are developed than can address the large numbers of genes and variants within them that, along with environmental and stochastic effects, result in the development of disease for a particular person.

scholarly journals An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Leandro de Araújo Lima ◽  
Ana Cecília Feio-dos-Santos ◽  
Sintia Iole Belangero ◽  
Ary Gadelha ◽  
Rodrigo Affonseca Bressan ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Integrative Approach ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Hyperactivity Disorder ◽  
New Genes

Abstract Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two “in silico” protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.

The Role of Copy Number Variation in Psychiatric Disorders

2018 ◽  
pp. 84-95
Author(s):  
Elliott Rees ◽  
George Kirov
Keyword(s):  
Autism Spectrum Disorders ◽  
Copy Number ◽  
Selection Pressure ◽  
Copy Number Variants ◽  
Autism Spectrum ◽  
High Odds ◽  
Strong Selection ◽  
Increase Risk ◽  
Number Variation

Copy number variants (CNVs) are deletions, duplications, inversions, or translocations of large DNA segments. They can play a significant role in human disease. Thirteen CNVs have received strong statistical support for involvement in schizophrenia. They are all rare in cases (<1%), much rarer among controls, and have high odds ratios (ORs) for causing disease. The same CNVs also increase risk for autism spectrum disorders, developmental delay, and medical/physical comorbidities. The penetrance of these CNVs for any disorder is relatively high, ranging from 10% for 15q11.2 deletions to nearly 100% for deletions at 22q11.2. Strong selection pressure operates against carriers of these CNVs. Most of these are formed by non-allelic homologous recombination (NAHR), which leads to high mutation rates, thus maintaining the rates of these CNVs in the general population, despite the strong selection forces.

Basic principles of genetic disease

ESC CardioMed ◽  
2018 ◽  
pp. 669-671
Author(s):  
Eric Schulze-Bahr
Keyword(s):  
Genetic Disease ◽  
Copy Number ◽  
Copy Number Variants ◽  
Single Nucleotide Variants ◽  
Individual Genome ◽  
Base Pairs ◽  
Single Nucleotide ◽  
Basic Principles ◽  
Bona Fide ◽  
Genomic Regions

The human genome consists of approximately 3 billion (3 × 109) base pairs of DNA (around 20,000 genes), organized as 23 chromosomes (diploid parental set), and a small mitochondrial genome (37 genes, including 13 proteins; 16,589 base pairs) of maternal origin. Most human genetic variation is natural, that is, common or rare (minor allele frequency >0.1%) and does not cause disease—apart from every true disease-causing (bona fide) mutation each individual genome harbours more than 3.5 million single nucleotide variants (including >10,000 non-synonymous changes causing amino acid substitutions) and 200–300 large structural or copy number variants (insertions/deletions, up to several thousands of base-pairs) that are non-disease-causing variations and scattered throughout coding and non-coding genomic regions.

scholarly journals Copy number variation of LINGO1 in familial dystonic tremor

2019 ◽  
Vol 5 (1) ◽  
pp. e307 ◽  
Author(s):  
Vafa Alakbarzade ◽  
Thomas Iype ◽  
Barry A. Chioza ◽  
Royana Singh ◽  
Gaurav V. Harlalka ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Gene Copy ◽  
Whole Genome ◽  
Snp Microarray ◽  
Dystonic Tremor ◽  
South Indian ◽  
Number Variation ◽  
Microarray Studies

ObjectiveTo elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor.MethodsWhole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals.ResultsWhole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire LINGO1 gene.ConclusionsThe identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional LINGO1 gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of LINGO1 as a potential pathogenic mechanism.

scholarly journals 30 Mutli-omic data integration in quantitative genetics

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 15-15
Author(s):  
Gota Morota
Keyword(s):  
Gene Expression ◽  
Data Integration ◽  
High Throughput ◽  
Quantitative Genetics ◽  
Copy Number ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Number Variation ◽  
Omic Data Integration ◽  
Omic Data

Abstract The advent of high-throughput technologies has generated diverse omic data including single-nucleotide polymorphisms, copy-number variation, gene expression, methylation, and metabolites. The next major challenge is how to integrate those multi-omic data for downstream analyses to enhance our biological insights. This emerging approach is known as multi-omic data integration, which is in contrast to studying each omic data type independently. I will discuss challenging issues in developing algorithms and methods for multi-omic data integration. The particular focus will be given to the potential for combining diverse types of FAANG data and the utility of multi-omic data integration in association analysis and phenotypic prediction.

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