ReviewMolecular psychiatry2009
The role of genetic variation in the causation of mental illness: an evolution-informed framework.
Review in Molecular psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.
- Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.Nature genetics · 2018Pooled it
- The serotonin transporter gene alters sensitivity to attention bias modification: evidence for a plasticity gene.Biological psychiatry · 2011Trial
- Gene-Environment Interaction of Rims1 and Adolescent Social Isolation on Schizophrenia-Like Behaviors in Mice.Neuroscience bulletin · 2026Article
- The DCIDE framework: systematic investigation of evolutionary hypotheses, exemplified with autism.Biological reviews of the Cambridge Philosophical Society · 2025Review
- Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.PloS one · 2025Article
- Asian-European differentiation of schizophrenia-associated genes driven by admixture and natural selection.iScience · 2024Article
- Co-fractionation-mass spectrometry to characterize native mitochondrial protein assemblies in mammalian neurons and brain.Nature protocols · 2023Article
- Cryptic mutations of PLC family members in brain disorders: recent discoveries and a deep-learning-based approach.Brain : a journal of neurology · 2023Review
- The Genetics of Intellectual Disability.Brain sciences · 2023Review
- Ultra-rare and common genetic variant analysis converge to implicate negative selection and neuronal processes in the aetiology of schizophrenia.Molecular psychiatry · 2022Article
- Antioxidative Defense Genes and Brain Structure in Youth Bipolar Disorder.The international journal of neuropsychopharmacology · 2022Article
- Methylation of the serotonin transporter gene moderates the depressive subjective effect of cocaine.Behavioural brain research · 2022Article
- Pharmacogenetics of Addiction Therapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Association of the Combined Effects between Insulin-Like Growth Factor-1 Gene Polymorphisms and Negative Life Events with Major Depressive Disorder among Chinese population in the Context of Oxidative Stress.Oxidative medicine and cellular longevity · 2022Article
- A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder.NPJ genomic medicine · 2021Article
- Identifying a novel biological mechanism for alcohol addiction associated with circRNA networks acting as potential miRNA sponges.Addiction biology · 2021Article
- Identification of a functional human-unique 351-bp Alu insertion polymorphism associated with major depressive disorder in the 1p31.1 GWAS risk loci.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Evolutionary Ecological Model of Defence Activation Disorders Via the Marginal Value Theorem.Psychiatry investigation · 2020Article
- No Evidence for Widespread Positive Selection Signatures in Common Risk Alleles Associated with Schizophrenia.Schizophrenia bulletin · 2020Article
- The genetics of depression: successful genome-wide association studies introduce new challenges.Translational psychiatry · 2019Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apparently large genetic contribution to the aetiology of mental illness presents a formidable puzzle. Unlike common physical disorders, mental illness usually has an onset early in the reproductive age and is associated with substantial reproductive disadvantage. Therefore, genetic variants associated with vulnerability to mental illness should be under strong negative selection pressure and be eliminated from the genetic pool through natural selection. Still, mental disorders are common and twin studies indicate a strong genetic contribution to their aetiology. Several theories have been advanced to explain the paradox of high heritability and reproductive disadvantage associated with the same common phenotype, but none provides a satisfactory explanation for all types of mental illness. At the same time, identification of the molecular substrate underlying the large genetic contribution to the aetiology of mental illness is proving more difficult than expected. The quest for genetic variants associated with vulnerability to mental illness is predicated upon the common disease/common variant (CDCV) hypothesis. On the basis of a summary of evidence, it is concluded that the CDCV hypothesis is untenable for most types of mental illness. An alternative evolution-informed framework is proposed, which suggests that gene-environment interactions and rare genetic variants constitute most of the genetic contribution to mental illness. Common mental illness with mild reproductive disadvantage is likely to have a large contribution from interactions between common genetic variants and environmental exposures. Severe mental illness that confers strong reproductive disadvantage is likely to have a large and pleiotropic contribution from rare variants of recent origin. This framework points to a need for a paradigm change in genetic research to enable major progress in elucidating the aetiology of mental illness.
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