Detailed project information

Current methods in behaviour genetics and genetic epidemiology generally assume that genes and environment act in an additive manner. For a number of traits and disorders this assumption works well in practice. For complex polygenic traits, however, assumptions of independent action of genes and environment may not hold and will seriously frustrate attempts at gene finding. An interaction between genes and the environmental factors that are shared between individuals will act to inflate the effects of genes, whereas an interaction between genes and idiosyncratic environmental factors will act as an environmental influence, and effectively reduce the power of all gene finding approaches. Further complications for gene finding arise, when genes and environment correlate due to, for instance, cultural transmission. Especially in the context of psychiatric diseases and complex traits such as cognitive ability, an additive view of genes and environment may be a costly oversimplification (Collins, et al., 2003).

I, therefore, propose to develop a methodological framework that allows the modelling of interaction and correlation between genes and environment. This framework will be applicable to designs in which environmental factors or genes have or have not been measured and can incorporate, in a single model, observations on multiple traits in offspring, parents and spouses. I will apply the developed methodological framework to data on cognitive ability, a highly heritable trait for which it has proven difficult to find the actual genes, and for which it is expected that the effects of genes and environment are not purely additive.

I hypothesize that accepting the reality of a complex interplay between genes and environment into our models will improve understanding of the sources of variation in complex traits, and increase the odds of identification of actual genes, where methods that fail to appreciate the role of the environment have not.

Articles

• DJA Smit (2005). Heritability of background EEG across the power spectrum. Psychophysiology. pp. 
• S van der Sluis (2006). Detecting genotype-environment interaction in monozygotic twin data: comparing the Jinks and Fulker test and a new test based on Marginal Maximum Likelihood estimation. Twin Res Hum Genet. pp. 
• K Silventoinen (2006). Genetic contributions to the association between height and intelligence: Evidence from Dutch twin data from childhood to middle age. Genes Brain Behav. pp. 
• D POSTHUMA (2006). Introduction to the special issue: human linkage studies for behavioral traits. Behav genet. pp. 
• D POSTHUMA (2006). Replicated linkage for eye color on 15q using comparative ratings of sibling pairs. Behav genet. pp. 
• MF Gosso (2006). The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts.. Mol Psychiat. pp. 
• TJ Polderman (2006). Genetic analyses of teacher ratings of problem behavior in 5-year-old twins. Twin Res Hum Genet. pp. 
• DI Boomsma (2006). Genetic linkage and association analysis for loneliness in Dutch twin and sibling pairs points to a region on chromosome 12q23-24. Behav genet. pp. 
• JM Vink (2006). Genome-wide linkage scan to identify Loci for age at first cigarette in Dutch sibling pairs. Behav genet. pp. 
• TJ Polderman (2006). A longitudinal twin study on IQ, executive functioning, and attention problems during childhood and early adolescence. Acta Neurol Belg. pp. 
• DI Boomsma (2006). Netherlands Twin Register: from twins to twin families. Twin Res Hum Genet. pp. 
• S Nieuwenhuis (2006). Accounting for sequential trial effects in the flanker task: conflict adaptation or associative priming?. Mem Cognit. pp. 
• N Mekel-Bobrov (2006). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Hum Mol Genet. pp. 
• CH Hillman (2006). Physical activity and cognitive function in a cross-section of younger and older community-dwelling individuals. health Psychol. pp. 
• MF Gosso (2006). Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families. Genes Brain Behav. pp. 
• HE Hulshoff Pol (2006). Genetic contributions to human brain morphology and intelligence.. J Neurosci. pp. 
• K Silventoinen (2006). Genetic and environmental factors affecting self-rated health from age 16-25: a longitudinal study of Finnish twins. Behav genet. pp. 
• M.F. Gosso, E.J.C. de Geus, M.J. van Belzen, T.J.C. Polderman, P. Heutink, D.I. Boomsma, Prof. dr. D. Posthuma (2006). The SNAP-25 gene is associated with cognitive ability: Evidence from a family based study in two independent Dutch cohorts.. Mol Psychiat. pp. 878-886
• M.F. Gosso, M.J. van Belzen, E.J.C. de Geus, J.C. Polderman, P. Heutink, D.I. Boomsma, Prof. dr. D. Posthuma (2006). Family based association testing provides further evidence for a role of the CHRM2 gene in cognition. . Genes Brain Behavior. pp. 577-584
• E.J.C. de Geus, Prof. dr. D. Posthuma (2006). Progress in the molecular genetic study of intelligence. Cur Dir Psych. pp. 151-155
• P.M. Visscher, G. Willemsen, G. Zhu, N.G. Martin, P.E. Slagboom, E.J.C. de Geus, D.I. Boomsma, Prof. dr. D. Posthuma (2006). Replicated linkage for eye color on 15q using comparative ratings of sibling pairs. Behav Genet. pp. 
• K. Silventoinen, E. Lahelma, R.J. Rose, J. Kaprio, Prof. dr. D. Posthuma (2006). Genetic and environmental factors affecting self-rated health from age 16 to 25: a longitudinal study of Finnish twins. Behav Genet, Published online 12 August 2006.. pp. online
• S. van der Sluis, C.V. Dolan, D.I. Boomsma, Prof. dr. D. Posthuma (2006). Detecting Genotype-Environment interaction in MZ twin data: the Jinks & Fulker test and a new test based on Marginal Maximum Likelihood estimation. Twin Research. pp. 
• C.V. Dolan, E.J.C. de Geus, R. Colum, D.I. Boomsma, S. van der Sluis, Prof. dr. D. Posthuma (2006). Sex differences on the Dutch WAIS-III.. Intelligence. pp. 273-289
• S. van der Sluis, C. Derom, E. Thiery, M. Bartels, T.J.C. Polderman, S. van Gestel, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Dr. N. Jacobs, Prof. dr. D. Posthuma, Prof. dr. F.C. Verhulst (2006). Sex differences on the WISC-R in Belgium and The Netherlands. . pp. 
• Prof. dr. D. Posthuma, P.M. Visscher, G. Zhu, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Prof. dr. N.G. Martin, Prof. dr. P.E. Slagboom, Ing. G. Willemsen (2006). Replicated linkage for eye color on 15q using comparative ratings of sibling pairs.. Behav Genet. pp. 12-7
• K. Silventoinen, M. Bartels, G.F. Willemsen, Dr. C.E.M. van Beijsterveldt, Prof. dr. D.I. Boomsma, Drs. G.F. Estourgie-van Burk, Prof. dr. D. Posthuma (2007). Genetic regulation of growth in height and weight from three to 12 years of age: a longitudinal study of Dutch twin children.. Twin Research Human Genetics. pp. 354-63
• K. Silventoinen, Prof. dr. D. Posthuma, E. Lahelma, R.J. Rose, Prof. J. Kaprio (2007). Genetic and environmental factors affecting self-rated from age 16 to 25: a longitudinal study of Finnish twins.. Behav Genet. pp. 326-333
• D.J. Smit, Prof. dr. D.I. Boomsma, Dr. E.J. de Geus, Prof. dr. D. Posthuma, Prof. dr. C.J. Stam (2007). Heritability of "small-world" networks in the brain: A graph theoretical analysis of resting-state EEG functional connectivity. Hum Brain Mapp. pp. 
• D.J.A. Smit, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Prof. dr. D. Posthuma (2007). Genetic contribution to the P3 in Young and Middle-aged Adult Subjects. Twin Research Human Genetics. pp. 335-47
• D.J.A. Smit, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Prof. dr. D. Posthuma (2007). The Relation between Frontal EEG Asymmetry and the Risk for Anxiety and Depression. Biol Psychol. pp. 26-33
• S.F. Thomsen, C.S. Ulrik, K.O. Kyvik, L.R. Skadhauge, I. Steffensen, C. Backer, Prof. dr. D. Posthuma, Prof. dr. T.I.A. Sorensen (2007). Associations between obesity and asthma in a large sample of twins. Allergy. pp. 1199-204
• S. van der Sluis, Prof. dr. C.V. Dolan, Prof. dr. M.C. Neale, Prof. dr. D. Posthuma (2007). Power Calculations Using Exact Data Simulation: A Useful Tool for Genetic Study Designs. Behav Genet.. pp. 
• A.D. Goedhart, S. van der Sluis, G. Willemsen, Prof. dr. E.J.C de Geus, Dr. ing. J.H. Houtveen (2007). Comparison of time and frequency domain measures of RSA in ambulatory recordings. Psychophysiology. pp. 203-215
• M.F. Gosso, T.J.C. Polderman, P. Heutink, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Prof. dr. D. Posthuma (2007). Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study. BMC Med Genet. pp. 
• M.F. Gosso, M. van Belzen, P. Heutink, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Dr. J.C. Polderman, Prof. dr. D. Posthuma (2007). Family based association testing provides further evidence for a role of the CHRM2 gene in cognition. . pp. 
• Drs. J.J. Hottenga, J.B. Withfield, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Prof. dr. N.G. Martin, Prof. dr. D. Posthuma, Ing. G. Willemsen (2007). Genome-wide scan for blood pressure in Australian and Dutch subjects suggests linkage at 5p, 14q and 17p.. . pp. 
• E.A.M. Kuijper, C.B. Lambalk, S. van der Sluis, Prof. dr. M.A. Blankenstein, Prof. dr. D.I. Boomsma, Prof. dr. E.J.C de Geus, Prof. dr. D. Posthuma (2007). Heritability of reproductive hormones in adult male twins.. Hum Reprod. pp. 2153-9
• N. Mekel-Bobrov, S.L. Gilbert, P. Lind, M. Luciano, S.E. Harris, M.F. Gosso, Prof. dr. D. Posthuma (2007). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Hum Mol Genet. pp. 600-8
• T.J.C. Polderman, Prof. dr. D.I. Boomsma, Dr. E.M. Derks, Prof. dr. J.J. Hudziak, Prof. dr. D. Posthuma, Prof. dr. F.C. Verhulst (2007). Across the continuum of Attention Skills: A twin study of the SWAN ADHD rating scale.. Journal of Child Psychology and Psychiatry. pp. 1080-1087
• T.J.C. Polderman, L.M.J. de Sonneville, Prof. dr. D.I. Boomsma, Prof. dr. D. Posthuma, Dr. J.F. Stins, Prof. dr. F.C. Verhulst (2007). Genetic analysis of the stability of executive functioning during childhood. Biological Psychology. pp. 11-20
• DJA Smit (2007). The relation between frontal EEG asymmetry and the risk for anxiety and depression. Biol Psychol. pp. 
• SF Thomsen (2007). Association between obesity and asthma in a twin cohort.. Allergy. pp. 
• M de Moor (2007). Genome-wide linkage scan for exercise participation in Dutch sibling pairs. Eur J Hum Genet. pp. 
• CM Middeldorp (2007). Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype. Mol Psychiat. pp. 
• DJA Smit (2007). Heritability of anterior and posterior visual N1. Int J Psychophysiol. pp. 
• TJ Polderman (2007). Genetic analyses of the stability of executive functioning during childhood. Biol Psychol. pp. 
• EA Kuijper (2007). Heritability of reproductive hormones in adult male twins. Hum Reprod. pp. 
• K Silventoinen (2007). Genetic regulation of growth in height and weight from 3 to 12 years of age: a longitudinal study of Dutch twin children. Twin Res Hum Genet. pp. 
• DJA Smit (2007). Genetic contribution to the P3 in young and middle-aged adults. Twin Res Hum Genet. pp. 
• JJ Hottenga (2007). Genome-wide scan for blood pressure in Australian and Dutch subjects suggests linkage at 5P, 14Q, and 17P. Hypertension. pp. 
• MF Gosso (2007). Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study. BMC Med Genet. pp. 
• TJ Polderman (2007). Across the continuum of attention skills: a twin study of the SWAN ADHD rating scale. J Child Psychol Psychiatry. pp. 
• MF Gosso (2008). Common variants underlying cognitive ability: further evidence for association between the SNAP-25 gene and cognition using a family-based study in two independent Dutch cohorts. Genes Brain Behav. pp. 
• Z Bochdanovits (2008). Functional polymorphism under positive evolutionary selection in ADRB2 is associated with human intelligence with opposite effects in the young and the elderly. Behav genet. pp. 
• MA Jonker (2008). Gamma frailty model for linkage analysis with application to interval-censored migraine data. Biostatistics. pp. 
• S van der Sluis (2008). Gene-environment interaction in adults' IQ scores: measures of past and present environment. Behav genet. pp. 
• M Luciano (2008). Testing replication of a 5-SNP set for general cognitive ability in six population samples. Eur J Hum Genet. pp. 
• S van der Sluis (2008). A general test for gene-environment interaction in sib pair-based association analysis of quantitative traits. Behav genet. pp. 
• EJC de Geus (2008). . Imaging the genetics of brain structure and function. Biol Psychol. pp. 
• DJA Smit (2008). Heritability of "small-world" networks in the brain: a graph theoretical analysis of resting-state EEG functional connectivity. Hum Brain Mapping. pp. 
• et al, dr D POSTHUMA (2009). A note on permutation tests for genetic association analysis of quantitative traits when variances are heterogeneous.. Genet Epidemiol. pp. 
• C Haworth (2009). The heritability of general cognitive ability increases linearly from childhood to young adulthood. Mol Psychiat. pp. 
• TJ Polderman (2009). Attention problems, inhibitory control, and intelligence index overlapping genetic factors: a study in 9-, 12-, and 18-year-old twins. Neuropsychology. Neuropsychology. pp. 
• C Haworth (2009). A twin study of the genetics of high cognitive ability selected from 11,000 twin pairs in six studies from four countries. Behav genet. pp. 
• AAE Vinkhuyzen (2009). The heritability of aptitude and exceptional talent across different domains in adolescents and young adults. Behav genet. pp. 
• SF Thomsen (2009). Exploring the association between severe respiratory syncytial virus infection and asthma: a registry-based twin study. J Respir Crit Care Med. pp. 
• DJA Smit (2009). Phenotypic and genetic correlations between evoked EEG/ERP measures during the response anticipation period of a delayed response task. Psychophysiology. pp. 
• L pardo (2009). . Global similarity with local differences in linkage disequilibrium between the Dutch and HapMap-CEU populations. Eur J Hum Genet. pp. 
• PF Sullivan (2009). Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo. Mol Psychiat. pp. 
• Z Bochdanovitz, et al (2009). A functional non-synonymous polymorphism under positive evolutionary selection in the beta-2 adrenergic receptor explains phenotypic differences in intelligence among humans. Behavior genetics. pp. 15-23
• et al, MHM de Moor (2009). Genome-wide association study of leisure-time exercise behavior in Dutch and American adults. Medicine & Science in Sports & Exercise. pp. epub-epub
• et al, R Brans (2010). Brain plasticity and intellectual ability are influenced by shared genes. J Neurosc. pp. 5519-5524
• et al, Haworth CMA (2010). The heritability of general cognitive ability increases linearly from childhood to young adulthood. Mol Psychiatry. pp. 1112-1120
• et al, D Ruano (2010). Functional gene-group analysis reveals a role of synaptic heterotrimeric G-proteins in cognitive ability. American Journal of Human Genetics. pp. 113-125
• DJA Smit, et al (2010). Endophenotypes in a dynamically connected brain. Behav Genet. pp. 167-177
• et al, S van der Sluis (2010). Sex differences in adults' motivation to achieve.. Intelligence. pp. 433-446
• S van der Sluis, et al (2010). Phenotypic complexity, poor phenotypic resolution, and measurement bias contribute to the missing heritability problem in genetic association studies.. Plos ONE. pp. 13929-13929
• AAE Vinkhuyzen, et al (2010). Individual differences in processing speed and working memory speed as assessed with the Sternberg memory scanning task.. Behavior Genetics. pp. 315-326
• D Posthuma, PM Visscher (2010). Statistical Power to Detect Genetic Loci Affecting Environmental Sensitivity. Behavior genetics. pp. 728-733
• et al, AAE Vinkhuyzen (2010). Genetic Influences on Environmental Factors. Genes, Brain Behavior. pp. 276-289
• Z Bochdanovitz, et al (2010). Joint re-analysis of twenty-nine correlated SNPs supports the role of PCLO/Piccolo as a causal risk factor for major depressive disorder. Mol Psychiatry. pp. 650-652
• et al, R Hoekstra (2011). Brief report: the construction and validation of an abridged version of the Autism-spectrum quotient (AQ-short).. J Autism Dev Disord. . pp. 589-596

Proefschriften

• AAE Vinkhuyzen (2010). General Cognitive Ability and the interplay between genes and environment. Vrije Universiteit Amsterdam. promotiedatum 1-11-2010

Bijdragen aan boeken

• D Posthuma, S van der Sluis, B Neale (2007). Single Locus Association Models. in: Dissection of complex trait variation through linkage and association. UK: . pp. 0-0
• D Posthuma, B Neale (2007). Variance Components Linkage Analysis for Quantitative Traits. in: Dissection of complex trait variation through linkage and association. UK: . pp. 0-0
• D Posthuma, DI Boomsma (2008). Intelligentieonderzoek bij tweelingen. in: Tweelingonderzoek ? Een fascinerende wetenschap. Amsterdam: . pp. 0-0
• D Posthuma, J DeLuca (2008). The Genetics of Information Processing Speed in Humans. in: Processing Speed in Clinical Populations. UK: . pp. 0-0
• Prof. dr. D. Posthuma, Prof. dr. E.J.C de Geus (2008). . in: The genetics of information processing speed in humans. : . pp. 
• Prof. dr. D. Posthuma (2008). . in: Intelligentieonderzoek bij tweelingen. : . pp. 
• Prof. dr. D. Posthuma, S. van der Sluis (2008). . in: Single Locus association models. : . pp. 
• Prof. dr. D. Posthuma, Prof. H.H. Maes (2008). . in: Variance components linkage analysis for Quantitative Traits. : . pp. 
• D Posthuma, Yong Kyu Kim (2009). Multivariate Genetic Analysis. in: Handbook of Behavior Genetics. US: . pp. 0-0
• D Posthuma, D Weinberger, T Goldberg (2009). The genetics of intelligence. in: The Genetics of Cognitive Neuroscience. US: . pp. 0-0
• D Posthuma, A Nelis, BJ Koops (2009). Zoek de verschillen & Over intelligentie, erfelijkheid en tweelingenonderzoek. in: de Maakbare Mens. Nijmegen: . pp. 0-0
• AAE Vinkhuyzen, D Posthuma, S van der Sluis, RA Carlstedt (2010). Behavior Genetics. in: Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research. US: . pp. 00-00