A whole genome association study of neuroticism using DNA pooling.
paper
Cited
Public
Unavailable
- Authors
- Shifman, S; Bhomra, A; Smiley, S; Wray, N R; James, M R; Martin, N G; Hettema, J M; An, S S; Neale, M C; van den Oord, E J C G; Kendler, K S; Chen, X; Boomsma, D I; Middeldorp, C M; Hottenga, J J; Slagboom, P E; Flint, J
- Year
- 2008
- Journal
- Molecular psychiatry
- PMID
- 17667963
- DOI
- 10.1038/sj.mp.4002048
- PMCID
- PMC4004964
We describe a multistage approach to identify single nucleotide polymorphisms (SNPs) associated with neuroticism, a personality trait that shares genetic determinants with major depression and anxiety disorders. Whole genome association with 452 574 SNPs was performed on DNA pools from approximately 2000 individuals selected on extremes of neuroticism scores from a cohort of 88 142 people from southwest England. The most significant SNPs were then genotyped on independent samples to replicate findings. We were able to replicate association of one SNP within the PDE4D gene in a second sample collected by our laboratory and in a family-based test in an independent sample; however, the SNP was not significantly associated with neuroticism in two other independent samples. We also observed an enrichment of low P-values in known regions of copy number variations. Simulation indicates that our study had approximately 80% power to identify neuroticism loci in the genome with odds ratio (OR)>2, and approximately 50% power to identify small effects (OR=1.5). Since we failed to find any loci accounting for more than 1% of the variance, the heritability of neuroticism probably arises from many loci each explaining much less than 1%. Our findings argue the need for much larger samples than anticipated in genetic association studies and that the biological basis of emotional disorders is extremely complex.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Emotional dysregulation, alexithymia and neuroticism: a systematic review on the genetic basis of a subset of psychological traits. | Castellini G et al. | β | 2023 | β |
| Recursive splicing is a rare event in the mouse brain. | Moon S et al. | β | 2022 | β |
| Variants in regulatory elements of PDE4D associate with major mental illness in the Finnish population. | Sinha V et al. | β | 2021 | β |
| Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits. | Datta D et al. | β | 2020 | β |
| Mammalian TRIM67 Functions in Brain Development and Behavior. | Boyer NP et al. | β | 2018 | β |
| The genetics of human personality. | Sanchez-Roige S et al. | β | 2018 | β |
| GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder. | Deckert J et al. | β | 2017 | β |
| Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism. | Kim SE et al. | β | 2017 | β |
| Anxiety as a neurodevelopmental disorder in a neuronal subpopulation: Evidence from gene expression data. | Viggiano A et al. | β | 2015 | β |
| Brain derived neurotrophic factor gene (BDNF) and personality traits: the modifying effect of season of birth and sex. | Kazantseva A et al. | β | 2015 | β |
| Genome-wide association studies in pharmacogenomics of antidepressants. | Lin E et al. | β | 2015 | β |
| GWA meta-analysis of personality in Korean cohorts. | Kim BH et al. | β | 2015 | β |
| An efficient and cost-effective approach for genic microsatellite marker-based large-scale trait association mapping: identification of candidate genes for seed weight in chickpea | Kujur A et al. | β | 2014 | β |
| Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory. | van den Berg SM et al. | β | 2014 | β |
| Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis. | Kaname T et al. | β | 2014 | β |
| Pharmacogenetics of second-generation antipsychotics. | Brennan MD | β | 2014 | β |
| The genetics of major depression. | Flint J et al. | β | 2014 | β |
| Anxiety genetics - findings from cross-species genome-wide approaches. | Sokolowska E et al. | β | 2013 | β |
| Biological psychiatry: time for new paradigms. | Linden D | β | 2013 | β |
| Cost-effective genome-wide estimation of allele frequencies from pooled DNA in Atlantic salmon (Salmo salar L.). | Ozerov M et al. | β | 2013 | β |
| First genome-wide association study on anxiety-related behaviours in childhood. | Trzaskowski M et al. | β | 2013 | β |
| Genome-wide association study of the five-factor model of personality in young Korean women. | Kim HN et al. | β | 2013 | β |
| Heritability and linkage analysis of personality in bipolar disorder. | Greenwood TA et al. | β | 2013 | β |
| Neuroticism and common mental disorders: meaning and utility of a complex relationship. | Ormel J et al. | β | 2013 | β |
| Performance of polygenic scores for predicting phobic anxiety. | Walter S et al. | β | 2013 | β |
| The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders. | Olivier JD et al. | β | 2013 | β |
| TMPRSS9 and GRIN2B are associated with neuroticism: a genome-wide association study in a European sample. | Aragam N et al. | β | 2013 | β |
| Association of genetic polymorphisms with personality profile in individuals without psychiatric disorders. | PeΕka-Wysiecka J et al. | β | 2012 | β |
| Different gene sets contribute to different symptom dimensions of depression and anxiety. | van Veen T et al. | β | 2012 | β |
| Genome-wide association study of temperament in bipolar disorder reveals significant associations with three novel Loci. | Greenwood TA et al. | β | 2012 | β |
| Meta-analysis of genome-wide association studies for personality. | de Moor MH et al. | β | 2012 | β |
| Polymorphisms in ABLIM1 are associated with personality traits and alcohol dependence. | Wang KS et al. | β | 2012 | β |
| Sex ratio dynamics and fluctuating selection on personality. | Del Giudice M | β | 2012 | β |
| Stress-sensitive neurosignalling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis. | van Eekelen JA et al. | β | 2012 | β |
| Support for involvement of glutamate decarboxylase 1 and neuropeptide Y in anxiety susceptibility. | Donner J et al. | β | 2012 | β |
| The challenges and promise of neuroimaging in psychiatry. | Linden DE | β | 2012 | β |
| The implications of genotype-environment correlation for establishing causal processes in psychopathology. | Jaffee SR et al. | β | 2012 | β |
| Common variants in DGKK are strongly associated with risk of hypospadias. | van der Zanden LF et al. | β | 2011 | β |
| Contributions of dopamine-related genes and environmental factors to highly sensitive personality: a multi-step neuronal system-level approach. | Chen C et al. | β | 2011 | β |
| Dissecting the genetic architecture of human personality. | MunafΓ² MR et al. | β | 2011 | β |
| Does variance in drinking motives explain the genetic overlap between personality and alcohol use disorder symptoms? A twin study of young women. | Littlefield AK et al. | β | 2011 | β |
| Genetics of emotion. | Bevilacqua L et al. | β | 2011 | β |
| Heritability of problem drinking and the genetic overlap with personality in a general population sample. | de Moor MH et al. | β | 2011 | β |
| Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. | Terracciano A et al. | β | 2011 | β |
| Neuroticism explained? From a non-informative vulnerability marker to informative person-context interactions in the realm of daily life. | Jacobs N et al. | β | 2011 | β |
| Nine-year stability of type D personality: contributions of genes and environment. | Kupper N et al. | β | 2011 | β |
| Personality Measurement and Assessment in Large Panel Surveys* | Roberts B et al. | β | 2011 | β |
| Predicting sensation seeking from dopamine genes: use and misuse of genetic prediction. | Powell JE et al. | β | 2011 | β |
| The efficacy of detecting variants with small effects on the Affymetrix 6.0 platform using pooled DNA. | Chiang CW et al. | β | 2011 | β |
| Advances in molecular genetics of panic disorder. | Maron E et al. | β | 2010 | β |
| A genome-wide association study of Cloninger's temperament scales: implications for the evolutionary genetics of personality. | Verweij KJ et al. | β | 2010 | β |
| A genome-wide association study of neuroticism in a population-based sample. | Calboli FC et al. | β | 2010 | β |
| An alternative to the search for single polymorphisms: toward molecular personality scales for the five-factor model. | McCrae RR et al. | β | 2010 | β |
| An association between Epac-1 gene variants and anxiety and depression in two independent samples. | Middeldorp CM et al. | β | 2010 | β |
| Attitudes and cardiovascular disease. | Tindle H et al. | β | 2010 | β |
| Differences in neuroticism and extraversion between patients with bipolar I or II and general population subjects or major depressive disorder patients. | JylhΓ€ P et al. | β | 2010 | β |
| Genome-wide association scan for five major dimensions of personality. | Terracciano A et al. | β | 2010 | β |
| Genome-wide association scan of trait depression. | Terracciano A et al. | β | 2010 | β |
| Genome-wide association studies: a powerful tool for neurogenomics. | Cowperthwaite MC et al. | β | 2010 | β |
| Imaging genetics: Progressing by leaps and bounds. | Pezawas L et al. | β | 2010 | β |
| Intermediate or brainless phenotypes for psychiatric research? | Meyer-Lindenberg A | β | 2010 | β |
| Modifiers of hearing impairment in humans and mice. | Yan D et al. | β | 2010 | β |
| Preconscious processing biases predict emotional reactivity to stress. | Fox E et al. | β | 2010 | β |
| Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders. | Juhasz G et al. | β | 2010 | β |
| The development of animal personality: relevance, concepts and perspectives. | Stamps J et al. | β | 2010 | β |
| The genetic and environmental relationship between major depression and the five-factor model of personality. | Kendler KS et al. | β | 2010 | β |
| Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays. | Schosser A et al. | β | 2010 | β |
| A comparison of association statistics between pooled and individual genotypes. | Knight J et al. | β | 2009 | β |
| Addiction genetics and pleiotropic effects of common haplotypes that make polygenic contributions to vulnerability to substance dependence. | Uhl GR et al. | β | 2009 | β |
| A genome-wide association study in 574 schizophrenia trios using DNA pooling. | Kirov G et al. | β | 2009 | β |
| An E3 ubiquitin ligase, Really Interesting New Gene (RING) Finger 41, is a candidate gene for anxiety-like behavior and beta-carboline-induced seizures. | Kim S et al. | β | 2009 | β |
| Association between genes of Disrupted in schizophrenia 1 (DISC1) interactors and schizophrenia supports the role of the DISC1 pathway in the etiology of major mental illnesses. | Tomppo L et al. | β | 2009 | β |
| Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited. | Rapoport J et al. | β | 2009 | β |
| CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms. | Juhasz G et al. | β | 2009 | β |
| Effects of catechol-O-methyltransferase on normal variation in the cognitive function of children. | Barnett JH et al. | β | 2009 | β |
| Genetic contributions to clinical pain and analgesia: avoiding pitfalls in genetic research. | Kim H et al. | β | 2009 | β |
| Genetics of anxiety and trauma-related disorders. | Norrholm SD et al. | β | 2009 | β |
| Genome-wide association study of acute post-surgical pain in humans. | Kim H et al. | β | 2009 | β |
| Imaging phenotypes of major depressive disorder: genetic correlates. | Savitz JB et al. | β | 2009 | β |
| Impact and quantification of the sources of error in DNA pooling designs. | Jawaid A et al. | β | 2009 | β |
| Linkage and association studies of anxiety disorders. | Hamilton SP | β | 2009 | β |
| Optimal DNA pooling-based two-stage designs in case-control association studies. | Zhao Y et al. | β | 2009 | β |
| Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene. | Hilgert N et al. | β | 2009 | β |
| Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance. | Blaya C et al. | β | 2009 | β |
| Public health significance of neuroticism. | Lahey BB | β | 2009 | β |
| The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression. | Montag C et al. | β | 2009 | β |
| The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity. | Distel MA et al. | β | 2009 | β |
| Visual perspective and genetics: a commentary on Lemogne and colleagues. | Sutin AR | β | 2009 | β |
| Addiction Reviews. Preface. | Uhl GR | β | 2008 | β |
| A genome-wide scan for Eysenckian personality dimensions in adolescent twin sibships: psychoticism, extraversion, neuroticism, and lie. | Gillespie NA et al. | β | 2008 | β |
| Evidence for associations between PDE4D polymorphisms and a subtype of neuroticism. | Heck A et al. | β | 2008 | β |
| Genetic approaches to addiction: genes and alcohol. | Ducci F et al. | β | 2008 | β |
| Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. | Shifman S et al. | β | 2008 | β |
| Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands. | Wray NR et al. | β | 2008 | β |
| Improving the prediction of treatment response in depression: integration of clinical, cognitive, psychophysiological, neuroimaging, and genetic measures. | Kemp AH et al. | β | 2008 | β |
| Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify "connectivity constellation" and drug target genes with pleiotropic effects. | Uhl GR et al. | β | 2008 | β |
| Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. | Lesch KP et al. | β | 2008 | β |
| Molecular genetics of anxiety in mice and men. | Hovatta I et al. | β | 2008 | β |
| Genetic boundary violations: phobic disorders and personality. | Smoller JW | β | 2007 | β |