scholarly journals Genetic cross-disorder analysis in psychiatry: from methodology to clinical utility

2019 ◽  
Vol 216 (5) ◽  
pp. 246-249 ◽  
Author(s):  
Dick Schijven ◽  
Jan H. Veldink ◽  
Jurjen J. Luykx
Keyword(s):  
Psychiatric Disorders ◽  
Clinical Utility ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Disease Aetiology ◽  
Genetic Cross

SummaryGenome-wide association studies have uncovered hundreds of loci associated with psychiatric disorders. Cross-disorder studies are among the prime ramifications of such research. Here, we discuss the methodology of the most widespread methods and their clinical utility with regard to diagnosis, prediction, disease aetiology and treatment in psychiatry.

scholarly journals Genome-wide association analysis reveals extensive genetic overlap between mood instability and psychiatric disorders but divergent patterns of genetic effects

2021 ◽  
Author(s):  
Guy Hindley ◽  
Kevin S O'Connell ◽  
Zillur Rahman ◽  
Oleksandr Frei ◽  
Shahram Bahrami ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Correlation ◽  
Association Studies ◽  
Single Gene ◽  
Genetic Effects ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Determinants ◽  
Mood Instability ◽  
Genome Wide

Mood instability (MOOD) is a transdiagnostic phenomenon with a prominent neurobiological basis. Recent genome-wide association studies found significant positive genetic correlation between MOOD and major depression (DEP) and weak correlations with other psychiatric disorders. We investigated the polygenic overlap between MOOD and psychiatric disorders beyond genetic correlation to better characterize putative shared genetic determinants. Summary statistics for schizophrenia (SCZ, n=105,318), bipolar disorder (BIP, n=413,466), DEP (n=450,619), attention-deficit hyperactivity disorder (ADHD, n=53,293) and MOOD (n=363,705), were analysed using the bivariate causal mixture model and conjunctional false discovery rate methods to estimate the proportion of shared variants influencing MOOD and each disorder, and identify jointly associated genomic loci. MOOD correlated positively with all psychiatric disorders, but with wide variation in strength (rg=0.10-0.62). Of 10.4K genomic variants influencing MOOD, 4K-9.4K were estimated to influence psychiatric disorders. MOOD was jointly associated with DEP at 163 loci, SCZ at 110, BIP at 60 and ADHD at 25, with consistent genetic effects in independent samples. Fifty-three jointly associated loci were overlapping across two or more disorders (transdiagnostic), seven of which had discordant effect directions on psychiatric disorders. Genes mapped to loci associated with MOOD and all four disorders were enriched in a single gene-set, synapse organization. The extensive polygenic overlap indicates shared molecular underpinnings across MOOD and psychiatric disorders. However, distinct patterns of genetic correlation and effect directions of shared loci suggest divergent effects on corresponding neurobiological mechanisms which may relate to differences in the core clinical features of each disorder.

scholarly journals Dissecting the phenotype in genome-wide association studies of psychiatric illness

2009 ◽  
Vol 195 (2) ◽  
pp. 97-99 ◽  
Keyword(s):  
Psychiatric Disorders ◽  
Psychiatric Illness ◽  
Genetic Architecture ◽  
Association Studies ◽  
Human Diseases ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
The Past ◽  
Genome Wide

SummaryOver the past 2 years genome-wide association studies have made major contributions to understanding the genetic architecture of many common human diseases. This editorial outlines the development of such studies in psychiatry and highlights the opportunities for advancing understanding of the biological underpinnings and nosological structure of psychiatric disorders.

scholarly journals Microbial Genome-Wide Association Studies: Lessons from Human GWAS

2016 ◽  
Author(s):  
Robert A. Power ◽  
Julian Parkhill ◽  
Tulio de Oliveira
Keyword(s):  
Disease Transmission ◽  
Drug Targets ◽  
Association Studies ◽  
Genome Wide Association ◽  
Microbial Genome ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Disease Aetiology ◽  
Number Of Microorganisms ◽  
Potential Drug Targets

AbstractThe reduced costs of sequencing have led to the availability of whole genome sequences for a large number of microorganisms, enabling the application of microbial genome wide association studies (GWAS). Given the successes of human GWAS in understanding disease aetiology and identifying potential drug targets, microbial GWAS is likely to further advance our understanding of infectious diseases. By building on the success of GWAS, microbial GWAS have the potential to rapidly provide important insights into pressing global health problems, such as antibiotic resistance and disease transmission. In this review, we outline the methodologies of GWAS, the state of the field of microbial GWAS today, and how lessons from GWAS can direct the future of the field.

Genome-wide association studies of psychiatric disorders

2008 ◽  
Author(s):  
G. Breen ◽  
I. Pedroso ◽  
S. Campos ◽  
P. McGuffin ◽  
D. Collier ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data

2016 ◽  
Author(s):  
Daniel S. Tylee ◽  
Jiayin Sun ◽  
Jonathan L. Hess ◽  
Muhammad A. Tahir ◽  
Esha Sharma ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Lupus Erythematosus ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Compulsive Disorder ◽  
Genome Wide ◽  
Heritability Estimation

AbstractIndividuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies (GWASs) to determine if commonly varying single nucleotide polymorphisms (SNPs) are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (HESS) methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn’s disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations amongst the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

scholarly journals miRNAs in NMDA receptor-dependent synaptic plasticity and psychiatric disorders

2016 ◽  
Vol 130 (14) ◽  
pp. 1137-1146 ◽  
Author(s):  
Hongmei Shen ◽  
Zheng Li
Keyword(s):  
Synaptic Plasticity ◽  
Psychiatric Disorders ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Aspartate Receptor ◽  
Genome Wide ◽  
Non Coding Rnas

The identification and functional delineation of miRNAs (a class of small non-coding RNAs) have added a new layer of complexity to our understanding of the molecular mechanisms underlying synaptic plasticity. Genome-wide association studies in conjunction with investigations in cellular and animal models, moreover, provide evidence that miRNAs are involved in psychiatric disorders. In the present review, we examine the current knowledge about the roles played by miRNAs in NMDA (N-methyl-D-aspartate) receptor-dependent synaptic plasticity and psychiatric disorders.

scholarly journals Genome-wide association studies in psychiatry: what have we learned?

2013 ◽  
Vol 202 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Ann L. Collins ◽  
Patrick F. Sullivan
Keyword(s):  
Psychiatric Disorders ◽  
Empirical Data ◽  
Genetic Architecture ◽  
Genetic Basis ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Considerable Effort ◽  
Genome Wide

SummaryGenome-wide association studies (GWAS) have been the focus of considerable effort in psychiatry. These efforts have markedly increased knowledge of the genetic basis of psychiatric disorders, and yielded empirical data on genetic architecture critical to addressing long-standing debates in the field. There is a now a clear path to increased knowledge of the ‘parts lists’ for these disorders.

scholarly journals Genome-Wide Association Study of Over 427,000 Individuals Establishes Executive Functioning as a Neurocognitive Basis of Psychiatric Disorders Influenced by GABAergic Processes

2019 ◽  
Author(s):  
Alexander S. Hatoum ◽  
Claire L. Morrison ◽  
Evann C. Mitchell ◽  
Max Lam ◽  
Chelsie E. Benca-Bachman ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Cognitive Processing ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Small Sample ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Genome Wide ◽  
The Uk

AbstractDeficits in executive functions (EFs), cognitive processes that control goal-directed behaviors, are associated with psychopathology and neurological disorders. Little is known about the molecular bases of EF individual differences; existing EF genome-wide association studies (GWAS) used small sample sizes and/or focused on individual tasks that are imprecise measures of EF. We conducted a GWAS of a Common EF (cEF) factor based on multiple tasks in the UK Biobank (N=427,037 European-descent individuals), finding 129 independent genome-wide significant lead variants in 112 distinct loci. cEF was associated with fast synaptic transmission processes (synaptic, potassium channel, and GABA pathways) in gene-based analyses. cEF was genetically correlated with measures of intelligence (IQ) and cognitive processing speed, but cEF and IQ showed differential genetic associations with psychiatric disorders and educational attainment. Results suggest that cEF is a genetically distinct cognitive construct that is particularly relevant to understanding the genetic variance in psychiatric disorders.

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