ReviewMolecular psychiatry2012
Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses.
Review in Molecular psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nature communications · 2018Pooled it
- The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis.Progress in neurobiology · 2015Pooled it
- The molecular genetic architecture of self-employment.PloS one · 2013Pooled it
- Genotype scores predict drug efficacy in subtypes of female sexual interest/arousal disorder: A double-blind, randomized, placebo-controlled cross-over trial.Women's health (London, England)Trial
- Article
- The molecular pathology of schizophrenia: an overview of existing knowledge and new directions for future research.Molecular psychiatry · 2023Review
- Rare genetic variants explain missing heritability in smoking.Nature human behaviour · 2022Article
- Inferring Gene-by-Environment Interactions with a Bayesian Whole-Genome Regression Model.American journal of human genetics · 2020Article
- Polygenic Architecture of Human Neuroanatomical Diversity.Cerebral cortex (New York, N.Y. : 1991) · 2020Article
- The Genetic Architecture of High Bone Mass.Frontiers in endocrinology · 2020Review
- Effects of Common and Rare Chromosome 4 GABAergic Gene Variation on Alcohol Use and Antisocial Behavior.Journal of studies on alcohol and drugs · 2019Article
- Using zebrafish to study skeletal genomics.Bone · 2019Review
- Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls.Psychological medicine · 2019Article
- Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders.Cell · 2019Review
- Harnessing Human Microphysiology Systems as Key Experimental Models for Quantitative Systems Pharmacology.Handbook of experimental pharmacology · 2019Article
- GWASinlps: non-local prior based iterative SNP selection tool for genome-wide association studies.Bioinformatics (Oxford, England) · 2019Article
- Genomic analysis of family data reveals additional genetic effects on intelligence and personality.Molecular psychiatry · 2018Article
- Signatures of negative selection in the genetic architecture of human complex traits.Nature genetics · 2018Article
- Whole genome sequence study of cannabis dependence in two independent cohorts.Addiction biology · 2018Article
- A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets.PLoS genetics · 2017Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
In this article, we review some of the data that contribute to our understanding of the genetic architecture of psychiatric disorders. These include results from evolutionary modelling (hence no data), the observed recurrence risk to relatives and data from molecular markers. We briefly discuss the common-disease common-variant hypothesis, the success (or otherwise) of genome-wide association studies, the evidence for polygenic variance and the likely success of exome and whole-genome sequencing studies. We conclude that the perceived dichotomy between 'common' and 'rare' variants is not only false, but unhelpful in making progress towards increasing our understanding of the genetic basis of psychiatric disorders. Strong evidence has been accumulated that is consistent with the contribution of many genes to risk of disease, across a wide range of allele frequencies and with a substantial proportion of genetic variation in the population in linkage disequilibrium with single-nucleotide polymorphisms (SNPs) on commercial genotyping arrays. At the same time, most causal variants that segregate in the population are likely to be rare and in total these variants also explain a significant proportion of genetic variation. It is the combination of allele frequency, effect size and functional characteristics that will determine the success of new experimental paradigms such as whole exome/genome sequencing to detect such loci. Empirical results suggest that roughly half the genetic variance is tagged by SNPs on commercial genome-wide chips, but that individual causal variants have a small effect size, on average. We conclude that larger experimental sample sizes are essential to further our understanding of the biology underlying psychiatric disorders.
Indexed as
Identifiers
21670730What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.