Research review: Polygenic methods and their application to psychiatric traits.
paper
Cited
Public
Unavailable
- Authors
- Wray, Naomi R; Lee, Sang Hong; Mehta, Divya; Vinkhuyzen, Anna A E; Dudbridge, Frank; Middeldorp, Christel M
- Year
- 2014
- Journal
- Journal of child psychology and psychiatry, and allied disciplines
- PMID
- 25132410
- DOI
- 10.1111/jcpp.12295
BACKGROUND: Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. METHODS AND SCOPE: We review the methods investigating the polygenic nature of complex disorders. We provide mini-guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs; a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still-missing heritability. FINDINGS: Genome-wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. Sample sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. CONCLUSIONS: Increasing the sample size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as sample sizes increase and as sample resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors.
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| Response to the Commentary on Maes et al. "A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents." | Maes HH et al. | β | 2017 | β |
| Sexual dimorphism in the genetic influence on human childlessness. | Verweij RM et al. | β | 2017 | β |
| Shared genetic influences between dimensional ASD and ADHD symptoms during child and adolescent development. | Stergiakouli E et al. | β | 2017 | β |
| The impact of genetics on future drug discovery in schizophrenia. | Matsumoto M et al. | β | 2017 | β |
| Using Clinical Characteristics to Identify Which Patients With Major Depressive Disorder Have a Higher Genetic Load for Three Psychiatric Disorders. | Verduijn J et al. | β | 2017 | β |
| Using information of relatives in genomic prediction to apply effective stratified medicine. | Lee SH et al. | β | 2017 | β |
| Using Polygenic Risk Scores to Establish Endophenotypes: Considerations and Current Constraints. | Glahn DC et al. | β | 2017 | β |
| Advances in the genetics of schizophrenia: toward a network and pathway view for drug discovery. | Collier DA et al. | β | 2016 | β |
| Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study. | Cuellar-Partida G et al. | β | 2016 | β |
| Attention deficit hyperactivity disorder. | Thapar A et al. | β | 2016 | β |
| Best Linear Unbiased Prediction of Individual Polygenic Susceptibility to Sporadic Vascular Dementia. | Lee C | β | 2016 | β |
| Common alleles contribute to schizophrenia in CNV carriers. | Tansey KE et al. | β | 2016 | β |
| Dependence of Gene-by-Environment Interactions (GxE) on Scaling: Comparing the Use of Sum Scores, Transformed Sum Scores and IRT Scores for the Phenotype in Tests of GxE. | Murray AL et al. | β | 2016 | β |
| Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women. | Mehta D et al. | β | 2016 | β |
| Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia. | Costas J et al. | β | 2016 | β |
| Genetic influences on adolescent behavior. | Dick DM et al. | β | 2016 | β |
| Genetic link between family socioeconomic status and children's educational achievement estimated from genome-wide SNPs. | Krapohl E et al. | β | 2016 | β |
| Genetics affects choice of academic subjects as well as achievement. | Rimfeld K et al. | β | 2016 | β |
| Genetics of Bipolar Disorder: Recent Update and Future Directions. | Goes FS | β | 2016 | β |
| Genome-wide analysis of over 106β000 individuals identifies 9 neuroticism-associated loci. | Smith DJ et al. | β | 2016 | β |
| Imagination in human social cognition, autism, and psychotic-affective conditions. | Crespi B et al. | β | 2016 | β |
| Impact of polygenic schizophrenia-related risk and hippocampal volumes on the onset of psychosis. | Harrisberger F et al. | β | 2016 | β |
| Increased rare duplication burden genomewide in patients with treatment-resistant schizophrenia. | Martin AK et al. | β | 2016 | β |
| Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia. | Benros ME et al. | β | 2016 | β |
| Is There a Female Protective Effect Against Attention-Deficit/Hyperactivity Disorder? Evidence From Two Representative Twin Samples. | Taylor MJ et al. | β | 2016 | β |
| Meta-analysis of genome-wide association studies of anxiety disorders. | Otowa T et al. | β | 2016 | β |
| New statistical approaches exploit the polygenic architecture of schizophrenia--implications for the underlying neurobiology. | Schork AJ et al. | β | 2016 | β |
| Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach. | Mooney MA et al. | β | 2016 | β |
| Personality Polygenes, Positive Affect, and Life Satisfaction. | Weiss A et al. | β | 2016 | β |
| Phenome-wide analysis of genome-wide polygenic scores. | Krapohl E et al. | β | 2016 | β |
| Polygenic dissection of major depression clinical heterogeneity. | Milaneschi Y et al. | β | 2016 | β |
| Polygenic Risk of Schizophrenia and Cognition in a Population-Based Survey of Older Adults. | Liebers DT et al. | β | 2016 | β |
| Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population. | Otto JM et al. | β | 2016 | β |
| SNP-based heritability estimates of the personality dimensions and polygenic prediction of both neuroticism and major depression: findings from CONVERGE. | Docherty AR et al. | β | 2016 | β |
| The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume. | Lupton MK et al. | β | 2016 | β |
| The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders. | Smoller JW | β | 2016 | β |
| Top 10 Replicated Findings From Behavioral Genetics. | Plomin R et al. | β | 2016 | β |
| Accuracy of Gene Scores when Pruning Markers by Linkage Disequilibrium. | Dudbridge F et al. | β | 2015 | β |
| Addressing the Genetics of Human Mental Health Disorders in Model Organisms. | McCammon JM et al. | β | 2015 | β |
| A Fast Method that Uses Polygenic Scores to Estimate the Variance Explained by Genome-wide Marker Panels and the Proportion of Variants Affecting a Trait. | Palla L et al. | β | 2015 | β |
| Child maltreatment, impulsivity, and antisocial behavior in African American children: Moderation effects from a cumulative dopaminergic gene index. | Thibodeau EL et al. | β | 2015 | β |
| Common genetic risk variants are associated with positive symptoms and decision-making ability in patients with schizophrenia. | Martin AK et al. | β | 2015 | β |
| Gene set analysis: A step-by-step guide. | Mooney MA et al. | β | 2015 | β |
| Genetic overlap between diagnostic subtypes of ischemic stroke. | Holliday EG et al. | β | 2015 | β |
| Genetics and brain morphology. | Strike LT et al. | β | 2015 | β |
| Genetics and intelligence differences: five special findings. | Plomin R et al. | β | 2015 | β |
| Genetics in child and adolescent psychiatry: methodological advances and conceptual issues. | Hohmann S et al. | β | 2015 | β |
| Genome-wide association study of schizophrenia in Ashkenazi Jews. | Goes FS et al. | β | 2015 | β |
| The importance of distinguishing between the odds ratio and the incidence rate ratio in GWAS. | Waltoft BL et al. | β | 2015 | β |
| Towards indicated prevention of psychosis: using probabilistic assessments of transition risk in psychosis prodrome. | Clark SR et al. | β | 2015 | β |
| Editorial perspective: Why is there such a mismatch between traditional heritability estimates and molecular genetic findings for behavioural traits? | Thapar A et al. | β | 2014 | β |
| The contribution of genetic variants to disease depends on the ruler. | Witte JS et al. | β | 2014 | β |
| The foundations of next generation attention-deficit/hyperactivity disorder neuropsychology: building on progress during the last 30Β years. | Sonuga-Barke EJ et al. | β | 2014 | β |