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1. Structural models of genome-wide covariance identify multiple common dimensions in autism

Author

Hoyos, L. de, Barendse, M.T., Schlag, F., Donkelaar, M.M.J. van, Verhoef, E., Shapland, C.Y., Klassmann, A., Buitelaar, J.K., Verhulst, B., Fisher, S.E., Rai, D., Pourcain, B. St, Hoyos, L. de, Barendse, M.T., Schlag, F., Donkelaar, M.M.J. van, Verhoef, E., Shapland, C.Y., Klassmann, A., Buitelaar, J.K., Verhulst, B., Fisher, S.E., Rai, D., and Pourcain, B. St

Abstract

Contains fulltext : 305225.pdf (Publisher’s version ) (Open Access), Common genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.

Published
2024

2. Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Author

Price, K.M., Wigg, K.G., Eising, E., Feng, Y, Blokland, K., Wilkinson, M., Kerr, E.N., Guger, S.L., Abbondanza, F., Allegrini, A.G., Andlauer, T.F.M., Bates, T.C., Bernard, M., Bonte, M., Boomsma, D.I., Bourgeron, T., Brandeis, D., Carreiras, M., Ceroni, F., Csépe, V., Dale, P.S., DeFries, J.C., Jong, P.F. de, Démonet, J.F., Zeeuw, E.L. de, Franken, M.-C.J., Francks, C., Gerritse, M.L., Gialluisi, A., Gordon, S.D., Gruen, J.R., Hayiou-Thomas, M.E., Hernández-Cabrera, J., Hottenga, J.-J., Hulme, C., Jansen, P.R., Kere, J., Koomar, T., Landerl, K., Leonard, G.T., Liao, Z., Luciano, M., Lyytinen, H., Martin, N.G., Martinelli, A., Maurer, U., Michaelson, J.J., Mirza-Schreiber, N., Moll, K., Monaco, A.P., Morgan, A.T., Müller-Myhsok, B., Newbury, D.F., Nöthen, M.M., Olson, R.K., Paracchini, S., Paus, T., Pausova, Z., Pennell, C.E., Pennington, B.F., Plomin, R.J., Ramus, F., Reilly, S., Richer, L., Rimfeld, K., Schulte-Körne, G., Shapland, C.Y., Simpson, N.H., Smith, S.D., Snowling, M.J., St Pourcain, B., Stein, J.F., Talcott, J.B., Tiemeier, H., Tomblin, J.B., Truong, D.T., Bergen, E. van, Schroeff, M.P. van der, Donkelaar, M.M.J. van, Verhoef, E., Wang, C.A., Watkins, K.E., Whitehouse, A.J.O., Willcutt, E.G., Wright, M.J., Zhu, G., Fisher, S.E., Lovett, M.W., Strug, L.J., Barr, C.L., University of St Andrews. School of Medicine, University of St Andrews. Centre for Biophotonics, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. Institute of Behavioural and Neural Sciences, University of St Andrews. St Andrews Bioinformatics Unit, University of St Andrews. Cellular Medicine Division, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Research Programs Unit, University of Helsinki, Consortium, Quantitative Trait Working Group of the GenLang, European Commission, Otorhinolaryngology and Head and Neck Surgery, Child and Adolescent Psychiatry / Psychology, RS: FPN CN 7, Language, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, LEARN! - Educational neuroscience, learning and development, and Human genetics

Subjects
Neuroinformatics, single nucleotide, Candidate gene, Autism Spectrum Disorder, Developmental dyslexia, autism spectrum disorder, QH426 Genetics, Polymorphism, Single Nucleotide, Neuronal migration, 3124 Neurology and psychiatry, polymorphism, Dyslexia, Cellular and Molecular Neuroscience, All institutes and research themes of the Radboud University Medical Center, problem solving, SDG 3 - Good Health and Well-being, dyslexia, Humans, Kiaa0319, Family, humans, Children, QH426, Problem Solving, Biological Psychiatry, MCC, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], genome-wide association study, Dyx1c1, Plasma-membrane, 3rd-DAS, Psychiatry and Mental health, Susceptibility, RC0321, SDG 4 - Quality Education, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Genome-Wide Association Study, Knockout mice
Abstract

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p~1.45 × 10–2, threshold = 2.5 × 10–2). For the GenLang Cohort (n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 × 10–2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q < 9.00 × 10–4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations., Translational Psychiatry, 12 (1), ISSN:2158-3188

Published
2022

3. Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, E., Mirza-Schreiber, N., Zeeuw, E.L. de, Wang, C.A., Truong, D.T., Allegrini, A.G., Shapland, C.Y., Zhu, G., Wigg, K.G., Gerritse, M.L., Molz, B., Alagöz, G., Gialluisi, A., Abbondanza, F., Rimfeld, K., Donkelaar, M.M.J. van, Liao, Z., Jansen, P.R., Andlauer, T.F.M., Bates, T.C., Bernard, M., Blokland, K., Bonte, M., Børglum, A.D., Bourgeron, T., Brandeis, D., Ceroni, F., Csépe, V., Dale, P.S., Jong, P.F. de, DeFries, J.C., Démonet, J.F., Demontis, D., Feng, Yu, Gordon, S.D.S., Guger, S.L., Hayiou-Thomas, M.E., Hernández-Cabrera, J.A., Hottenga, J.J., Hulme, C., Kere, J., Kerr, E.N., Koomar, T., Landerl, K., Leonard, G.T., Lovett, M.W., Lyytinen, H., Martin, N.G., Martinelli, A., Maurer, U., Michaelson, J.J., Moll, K., Monaco, A.P., Morgan, A.T., Nöthen, M.M., Pausova, Z., Pennell, C.E., Pennington, B.F., Price, K.M., Rajagopal, V.M., Ramus, F., Richer, L., Simpson, N.H., Smith, S.D., Snowling, M.J., Stein, J., Strug, L.J., Talcott, J.B., Tiemeier, H., Schroeff, M.P. van der, Verhoef, E., Watkins, K.E., Wilkinson, M., Wright, M.J., Barr, C.L., Boomsma, D.I., Carreiras, M., Franken, M.J., Gruen, J.R., Luciano, M., Müller-Myhsok, B., Newbury, D.F., Olson, R.K., Paracchini, S., Paus, T., Plomin, R., Reilly, S., Schulte-Körne, G., Tomblin, J.B., Bergen, E. van, Whitehouse, A.J.O., Willcutt, E.G., Pourcain, B. St, Francks, C., Fisher, S.E., St Pourcain, B., Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Human genetics, APH - Aging & Later Life, APH - Mental Health, Biological Psychology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Reproduction & Development, APH - Methodology, LEARN! - Educational neuroscience, learning and development, Child and Adolescent Psychiatry / Psychology, Otorhinolaryngology and Head and Neck Surgery, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Research Programs Unit, University of Helsinki, Language, RS: FPN CN 7, The Royal Society, University of St Andrews. Cellular Medicine Division, University of St Andrews. School of Medicine, University of St Andrews. Centre for Biophotonics, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. Institute of Behavioural and Neural Sciences, and University of St Andrews. St Andrews Bioinformatics Unit

Subjects
Neuroinformatics, Adult, kieli ja kielet, Adolescent, Individuality, QH426 Genetics, Polymorphism, Single Nucleotide, lukeminen, Language in Interaction, Young Adult, SDG 3 - Good Health and Well-being, RA0421, reading, RA0421 Public health. Hygiene. Preventive Medicine, Humans, Speech, study, Polymorphism, Reading j, Preschool, Child, QH426, perinnöllisyys, Genome-wide Association Study, Language, Meta-analysis, Reading, MCC, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], genome-wide association study, language, Multidisciplinary, meta-analyysi, 1184 Genetics, developmental biology, physiology, kielitaito, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, DAS, Single Nucleotide, meta-analysis, Genetic Loci, Child, Preschool, Genome-Wide Association Study, perimä, lukutaito, genome-wide association, SDG 4 - Quality Education
Abstract

Published August 23, 2022 The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 1028) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits. We thank all the children, twins, families, and participants who took part and are taking part in the 22 cohorts whose data contributed to these GWAS meta-analyses; the staff working on the different cohorts, including volunteers, study coordinators, interviewers, teachers, nurses, research scientists, general practitioners, midwives, psychologists, psychometrists, computer and laboratory technicians, and colleagues who assisted in the quality control and preparation of the imputed GWAS data; and the pharmacies and hospitals that were involved. B.M., B.M.-M., B.S.P., C.F., E.E., E.V., G.A., M.v.D., and S.E.F. are supported by the Max Planck Society. A.G. and T.F.M.A. were supported by the Munich Cluster for Systems Neurology (SyNergy), and A.G. was supported by Fondazione Umberto Veronesi. A.T.M. is supported by National Health and Medical Research Council of Australia (NHMRC) Grants 1105008 and 1195955 and Centre of Research Excellence Grant 1116976. A.J.O.W. is supported by NHMRC Grant 1173896. B.S.P. is supported by Simons Foundation Autism Research Initiative Grant 514787. C.Y.S. works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/3). D.I.B. acknowledges Royal Netherlands Academy of Science Professor Award PAH/6635. E.E. is supported by NIH Grant R01DC016977. E.G.W. and J.R.G. are supported by National Institute of Child Health and Human Development (NICHD) Grant P50 HD 27802. F.R. is supported by Agence Nationale de la Recherche Grants ANR-06-NEURO-019-01, ANR-17-EURE-0017 IEC, ANR-10-IDEX-0001-02 PSL, and ANR-11-BSV4-014-01 and European Commission Grant LSHM-CT-2005-018696. H.T. is supported by the Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) Grant VICI 016.VICI.170.200. J.C.D. was supported by NICHD Grant P50 HD 27802. J.J.M., J.B.To., and T.K. were supported by NIH Grant R01 DC014489. K.M.P. was supported by the Hospital for Sick Children Research Training Program (Restracomp). K.R. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (213514/Z/18/Z). M.J.S. is supported by Wellcome Trust Grant WT082032MA. S.P. and F.A. are supported by Royal Society Grants UF150663 and RGF\EA\180141. T.B. is supported by Institut Pasteur, the Bettencourt-Schueller Foundation, and Université de Paris. The Adolescent Brain Cognitive Development Study is supported by the NIH and additional federal partners (NIH Grants U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, and U24DA041147). The Aston Cohort was supported by funding from European Union (EU) Horizon 2020 Programme 641652 and Waterloo Foundation Grant 797/17290. The St. Andrews Bioinformatics Unit is funded by Wellcome Trust Grants 105621/Z/14/Z and 204821/Z/16/Z. ALSPAC is supported by UK Medical Research Council and Wellcome Grant 217065/Z/19/Z and the University of Bristol. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The Basque Center on Cognition, Brain and Language (BCBL) cohort was supported by the Basque Government through the Basic Excellence Research Centre program and the Agencia Estatal de Investigación through BCBL Severo Ochoa excellence accreditation. The Brisbane Adolescent Twin Sample was supported by Australian Research Council Grants A7960034, A79906588, A79801419, DP0212016, and DP0343921, with genotyping funded by the NHMRC Grant 389891. The Colorado Learning Disabilities Research Center cohort was supported by NICHD Grant P50 HD 27802. The Early Language in Victoria Study was supported by NHMRC Grant 436958. The Familial Influences on Literacy Abilities cohort is supported by the University of Amsterdam, the Max Planck Institue Nijmegen, and NWO Grants Rubicon 446-12-005 and VENI 451-15-017. The GRaD study was funded by the Manton Foundation, NIH Grants P50-HD027802 and K99-HD094902, and the Lambert Family. NeuroDys was funded by an EU Sixth Framework Program grant to the NeuroDys Consortium, Swiss National Science Foundation Grant 32-108130, and Austrian Science Fund Grant 18351-B02. The Netherlands Twin Register is funded by NWO Grants 480-04-004, 481-08-011, 056-32-010, 024.001.003, 480-15-001/674, 184.021.007, 184.033.111, and 56-464-14192; ZonMW Grants 911-09-032 and 912-10-020; the Amsterdam Public Health and Amsterdam Reproduction and Development Research Institutes; European Science Council Grant ERC Advanced 230374; EU Seventh Framework Program (FP7) Grant FP7/2007-2013: 602768; National Institute of Mental Health (NIMH) Grants U24 MH068457-06, R01 MH58799-03, and 1RC2 MH089995; and the Avera Institute for Human Genetics. The Pediatric Imaging, Neurocognition, and Genetics cohort is funded by NIH Grant RC2DA029475, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver NICHD. The Philadelphia Neurodevelopmental Cohort is funded by NIH Grants RC2MH089983 and RC2MH089924, an institutional development award to the Center for Applied Genomics from The Children’s Hospital of Philadelphia, and a donation from Adele and Daniel Kubert and thanks the NIH data repository. The Raine study was supported by long-term funding from NHMRC Grants 572613, 403981, and 1059711 and Canadian Institutes of Health Research (CIHR) Grant MOP-82893. Funding was also provided by the University of Western Australia, Curtin University, the Women and Infants Research Foundation, the Telethon Kids Institute, Edith Cowan University, Murdoch University, the University of Notre Dame Australia, and the Raine Medical Research Foundation. The Raine study analyses were supported by the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia. The Saguenay Youth Study is supported by the CIHR, the Heart and Stroke Foundation of Quebec, and the Canadian Foundation for Innovation. The SLI Consortium was funded by Wellcome Trust Grant 076566 and UK Medical Research Council Grant G1000569. The Twins Early Development Study is supported by UK Medical Research Council Grants MR/V012878/1 and MR/M021475/1, NIH Grant AG046938, and the EU FP7 grant FP7/2007-2013/: 602768. Toronto was supported by CIHR Grant MOP-133440. UK Dyslexia was supported by Wellcome Trust Grants 076566/Z/05/Z and 075491/Z/04, Waterloo Foundation Grant 797–1720, EU Grant 018696, and Royal Society Grant UF100463. The York cohort was funded by Wellcome Trust Grant 082036/B/07/Z. We acknowledge iPSYCH for sharing their summary statistics. The iPSYCH team was supported by Lundbeck Foundation Grants R102-A9118, R155-2014-1724, and R248-2017-2003; NIMH Grant 1U01MH109514-01; and the Universities and University Hospitals of Aarhus and Copenhagen. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, Aarhus University, Denmark.

Published
2022

4. Genomic contributions to infant and toddler vocabulary scores: Implications for association with health-, cognition-, and behaviour-related outcomes

Author

Verhoef, E., Allegrini, A., Jansen, P., Lange, K., Wang, C., Morgan, A., Ahluwalia, T., Symeonides, C., Eagle working group, Bisgaard, H., Eising, E., Franken, M., Hypponen, E., Mansell, T., Olislagers, M., Omerovic, E., Rimfeld, K., Schlag, F., Selzam, S., Shapland, C., Tiemeier, H., Whitehouse, A., Saffery, R., Bønnelykke, K., Reilly, S., Pennell, C., Wake, M., Cecil, C., Plomin, R., Fisher, S., and St Pourcain, B.

Published
2022

5. Polygenic risk for mental disorder reveals distinct association profiles across social behaviour in the general population

Author

Schlag, F.H., Allegrini, A.G., Buitelaar, J.K., Verhoef, E., Donkelaar, M.M.J. van, Plomin, R., Rimfeld, K., Fisher, S.E., St Pourcain, B., Schlag, F.H., Allegrini, A.G., Buitelaar, J.K., Verhoef, E., Donkelaar, M.M.J. van, Plomin, R., Rimfeld, K., Fisher, S.E., and St Pourcain, B.

Abstract

Contains fulltext : 251382.pdf (Publisher’s version ) (Open Access), Many mental health conditions present a spectrum of social difficulties that overlaps with social behaviour in the general population including shared but little characterised genetic links. Here, we systematically investigate heterogeneity in shared genetic liabilities with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), bipolar disorder (BP), major depression (MD) and schizophrenia across a spectrum of different social symptoms. Longitudinally assessed low-prosociality and peer-problem scores in two UK population-based cohorts (4-17 years; parent- and teacher-reports; Avon Longitudinal Study of Parents and Children(ALSPAC): N ≤ 6,174; Twins Early Development Study(TEDS): N ≤ 7,112) were regressed on polygenic risk scores for disorder, as informed by genome-wide summary statistics from large consortia, using negative binomial regression models. Across ALSPAC and TEDS, we replicated univariate polygenic associations between social behaviour and risk for ADHD, MD and schizophrenia. Modelling variation in univariate genetic effects jointly using random-effect meta-regression revealed evidence for polygenic links between social behaviour and ADHD, ASD, MD, and schizophrenia risk, but not BP. Differences in age, reporter and social trait captured 45-88% in univariate effect variation. Cross-disorder adjusted analyses demonstrated that age-related heterogeneity in univariate effects is shared across mental health conditions, while reporter- and social trait-specific heterogeneity captures disorder-specific profiles. In particular, ADHD, MD, and ASD polygenic risk were more strongly linked to peer problems than low prosociality, while schizophrenia was associated with low prosociality only. The identified association profiles suggest differences in the social genetic architecture across mental disorders when investigating polygenic overlap with population-based social symptoms spanning 13 years of child and adolescent development.

Published
2022

6. Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Author

Eising, E, Mirza-Schreiber, N, de Zeeuw, EL, Wang, CA, Truong, DT, Allegrini, AG, Shapland, CY, Zhu, G, Wigg, KG, Gerritse, ML, Molz, B, Alagoz, G, Gialluisi, A, Abbondanza, F, Rimfeld, K, van Donkelaar, M, Liao, Z, Jansen, PR, Andlauer, TFM, Bates, TC, Bernard, M, Blokland, K, Bonte, M, Borglum, AD, Bourgeron, T, Brandeis, D, Ceronihh, F, Csepe, V, Dale, PS, de Jong, PF, DeFries, JC, Demonet, J-F, Demontis, D, Feng, Y, Gordon, SD, Guger, SL, Hayiou-Thomas, ME, Hernandez-Cabrera, JA, Hottenga, J-J, Hulme, C, Kere, J, Kerr, EN, Koomar, T, Landerl, K, Leonard, GT, Lovett, MW, Lyytinen, H, Martin, NG, Martinelli, A, Maurer, U, Michaelson, JJ, Moll, K, Monaco, AP, Morgan, AT, Nothen, MM, Pausova, Z, Pennell, CE, Pennington, BF, Price, KM, Rajagopal, VM, Ramus, F, Richer, L, Simpson, NH, Smith, SD, Snowling, MJ, Stein, J, Struguuu, LJ, Talcott, JB, Tiemeier, H, van der Schroeff, MP, Verhoef, E, Watkins, KE, Wilkinson, M, Wright, MJ, Barr, CL, Boomsma, D, Carreiras, M, Franken, M-CJ, Gruen, JR, Luciano, M, Muller-Myhsok, B, Newbury, DF, Olson, RK, Paracchini, S, Paus, T, Plomin, R, Reilly, S, Schulte-Korn, G, Tomblin, JB, Bergen, E, Whitehouse, AJO, Willcutt, EG, St Pourcain, B, Francks, C, Fisher, SE, Eising, E, Mirza-Schreiber, N, de Zeeuw, EL, Wang, CA, Truong, DT, Allegrini, AG, Shapland, CY, Zhu, G, Wigg, KG, Gerritse, ML, Molz, B, Alagoz, G, Gialluisi, A, Abbondanza, F, Rimfeld, K, van Donkelaar, M, Liao, Z, Jansen, PR, Andlauer, TFM, Bates, TC, Bernard, M, Blokland, K, Bonte, M, Borglum, AD, Bourgeron, T, Brandeis, D, Ceronihh, F, Csepe, V, Dale, PS, de Jong, PF, DeFries, JC, Demonet, J-F, Demontis, D, Feng, Y, Gordon, SD, Guger, SL, Hayiou-Thomas, ME, Hernandez-Cabrera, JA, Hottenga, J-J, Hulme, C, Kere, J, Kerr, EN, Koomar, T, Landerl, K, Leonard, GT, Lovett, MW, Lyytinen, H, Martin, NG, Martinelli, A, Maurer, U, Michaelson, JJ, Moll, K, Monaco, AP, Morgan, AT, Nothen, MM, Pausova, Z, Pennell, CE, Pennington, BF, Price, KM, Rajagopal, VM, Ramus, F, Richer, L, Simpson, NH, Smith, SD, Snowling, MJ, Stein, J, Struguuu, LJ, Talcott, JB, Tiemeier, H, van der Schroeff, MP, Verhoef, E, Watkins, KE, Wilkinson, M, Wright, MJ, Barr, CL, Boomsma, D, Carreiras, M, Franken, M-CJ, Gruen, JR, Luciano, M, Muller-Myhsok, B, Newbury, DF, Olson, RK, Paracchini, S, Paus, T, Plomin, R, Reilly, S, Schulte-Korn, G, Tomblin, JB, Bergen, E, Whitehouse, AJO, Willcutt, EG, St Pourcain, B, Francks, C, and Fisher, SE

Abstract

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

Published
2022

7. Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Author

Price, KM, Wigg, KG, Eising, E, Feng, Y, Blokland, K, Wilkinson, M, Kerr, EN, Guger, SL, Abbondanza, F, Allegrini, AG, Andlauer, TFM, Bates, TC, Bernard, M, Bonte, M, Boomsma, DI, Bourgeron, T, Brandeis, D, Carreiras, M, Ceroni, F, Csepe, V, Dale, PS, DeFries, JC, de Jong, PF, Demonet, JF, de Zeeuw, EL, Franken, M-CJ, Francks, C, Gerritse, M, Gialluisi, A, Gordon, SD, Gruen, JR, Hayiou-Thomas, ME, Hernandez-Cabrera, J, Hottenga, J-J, Hulme, C, Jansen, PR, Kere, J, Koomar, T, Landerl, K, Leonard, GT, Liao, Z, Luciano, M, Lyytinen, H, Martin, NG, Martinelli, A, Maurer, U, Michaelson, JJ, Mirza-Schreiber, N, Moll, K, Monaco, AP, Morgan, AT, Mueller-Myhsok, B, Newbury, DF, Noethen, MM, Olson, RK, Paracchini, S, Paus, T, Pausova, Z, Pennell, CE, Pennington, BF, Plomin, RJ, Ramus, F, Reilly, S, Richer, L, Rimfeld, K, Schulte-Korne, G, Shapland, CY, Simpson, NH, Smith, SD, Snowling, MJ, St Pourcain, B, Stein, JF, Talcott, JB, Tiemeier, H, Tomblin, JB, Truong, DT, van Bergen, E, van der Schroeff, MP, Van Donkelaar, M, Verhoef, E, Wang, CA, Watkins, KE, Whitehouse, AJO, Willcutt, EG, Wright, MJ, Zhu, G, Fisher, SE, Lovett, MW, Strug, LJ, Barr, CL, Price, KM, Wigg, KG, Eising, E, Feng, Y, Blokland, K, Wilkinson, M, Kerr, EN, Guger, SL, Abbondanza, F, Allegrini, AG, Andlauer, TFM, Bates, TC, Bernard, M, Bonte, M, Boomsma, DI, Bourgeron, T, Brandeis, D, Carreiras, M, Ceroni, F, Csepe, V, Dale, PS, DeFries, JC, de Jong, PF, Demonet, JF, de Zeeuw, EL, Franken, M-CJ, Francks, C, Gerritse, M, Gialluisi, A, Gordon, SD, Gruen, JR, Hayiou-Thomas, ME, Hernandez-Cabrera, J, Hottenga, J-J, Hulme, C, Jansen, PR, Kere, J, Koomar, T, Landerl, K, Leonard, GT, Liao, Z, Luciano, M, Lyytinen, H, Martin, NG, Martinelli, A, Maurer, U, Michaelson, JJ, Mirza-Schreiber, N, Moll, K, Monaco, AP, Morgan, AT, Mueller-Myhsok, B, Newbury, DF, Noethen, MM, Olson, RK, Paracchini, S, Paus, T, Pausova, Z, Pennell, CE, Pennington, BF, Plomin, RJ, Ramus, F, Reilly, S, Richer, L, Rimfeld, K, Schulte-Korne, G, Shapland, CY, Simpson, NH, Smith, SD, Snowling, MJ, St Pourcain, B, Stein, JF, Talcott, JB, Tiemeier, H, Tomblin, JB, Truong, DT, van Bergen, E, van der Schroeff, MP, Van Donkelaar, M, Verhoef, E, Wang, CA, Watkins, KE, Whitehouse, AJO, Willcutt, EG, Wright, MJ, Zhu, G, Fisher, SE, Lovett, MW, Strug, LJ, and Barr, CL

Abstract

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)-GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p~1.45 × 10-2, threshold = 2.5 × 10-2). For the GenLang Cohort (n = 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q = 1.02 × 10-2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n = 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q < 9.00 × 10-4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations.

Published
2022

11. The genetic architecture of the human cerebral cortex

Author

Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Ching, C.R.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., Medland, S.E., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Ching, C.R.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., and Medland, S.E.

Abstract

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When co

Published
2020

12. Emergent hypercongestion in Vickrey bottleneck networks

Author

Frascaria, D. (Dario), Olver, N.K. (Neil), Verhoef, E. (Erik), Frascaria, D. (Dario), Olver, N.K. (Neil), and Verhoef, E. (Erik)

Abstract

Hypercongestion—the phenomenon that higher traffic densities can reduce throughput—is well understood at the link level, but has also been observed in a macroscopic form at the level of traffic networks; for instance, in morning rush-hour traffic into a downtown core. In this paper, we show that macroscopic hypercongestion can occur as a purely emergent effect of dynamic equilibrium behavior on a network, even if the underlying link dynamics (we consider Vickrey bottlenecks with spaceless vertical queues) do not exhibit hypercongestion.

Published
2020
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13. The genetic architecture of the human cerebral cortex

Author

Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, Medland, SE, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, and Medland, SE

Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

18. Domestic Market Power in the International Airline Industry

Author

Gerben de Jong, Behrens, C. L., Hester van Herk, Verhoef, E. T., Marketing, Spatial Economics, and Amsterdam Business Research Institute

Subjects
price discrimination, L13, R40, market power, ddc:330, L11, L93, international aviation, airline competition
Abstract

We posit and empirically test the hypothesis that airlines are able to charge a fare premium in markets that originate in their domestic country relative to similar markets that originate in foreign countries. To this end, we focus on intercontinental one-stop air travel trips for which the main, intercontinental, flight legs are identical, while the feeder legs depart from a mixture of domestic- and foreign origins. We collect a unique database of published fares for such trips and estimate reduced form fare regressions with main flight leg fixed effects. We find that trips from and to domestic airports (compared with foreign airports) are characterized by about 9.5 per cent higher fares, even after adding controls for airport dominance, trip operating costs, the competitive environment and origin catchment area characteristics. These findings demonstrate that airlines have substantial domestic market power, enabling them to raise fares at their domestic airports irrespective of aforementioned market conditions. The magnitude of this domestic country effect is large relative to the traditional airport dominance effect, suggesting that the distinction between domestic- and foreign origins is a crucial determinant of the degree of market power that airlines can exert in the international airline industry.

Published
2017

19. Private Road Supply in Networks with Heterogeneous Users

Author

Xinying Fu, Vincent A.C. van den Berg, Verhoef, E. T., Spatial Economics, and Tinbergen Institute

Subjects
R41, Congestion Pricing, R42, ddc:330, Private Supply, R48, Heterogeneity, Bottleneck Model
Abstract

We study different mixes of private and public supply of roads in a network with bottleneck congestion and heterogeneous users. In our setting, there are two parallel links for one origin and destination pair and two groups of travellers, where the group with higher value of time also has higher schedule delay value. Previously scholars have argued that as travellers become more heterogeneous, they benefit more from product differentiation, and thus private supply of roads becomes more efficient. However, we find that local monopoly power might also increase, i.e. the private supplier can increase the toll on his link without worrying that travellers will move to the other link. This can undermine the efficiency of private supply of roads. The problem is especially severe with flat tolls, where travellers in equilibrium tend to travel on separate roads. With queue-eliminating tolls, however, both types tend to travel on both roads in equilibrium, and the competition between road providers remains relatively intense.

Published
2017

20. Imaging genetics in neurodevelopmental psychopathology.

Author

Klein, M., Donkelaar, M.M.J. van, Verhoef, E., Franke, B., Klein, M., Donkelaar, M.M.J. van, Verhoef, E., and Franke, B.

Abstract

Contains fulltext : 208443.pdf (publisher's version ) (Closed access)

Published
2017

21. CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer

Author

Zoni, E, primary, Chen, L, additional, Karkampouna, S, additional, Granchi, Z, additional, Verhoef, E I, additional, La Manna, F, additional, Kelber, J, additional, Pelger, R C M, additional, Henry, M D, additional, Snaar-Jagalska, E, additional, van Leenders, G J L H, additional, Beimers, L, additional, Kloen, P, additional, Gray, P C, additional, van der Pluijm, G, additional, and Kruithof-de Julio, M, additional

Published
2017
Full Text
View/download PDF

23. Ruimtelijke economie

Author

Elhorst, Jean, Van Oort, F., Verhoef, E, Phlippen, S., Werner, G., and Economics, Econometrics and Finance

Published
2015

24. Private Road Networks with Uncertain Demand

Author

Fu, X., Vincent A.C. van den Berg, Verhoef, E. T., and Spatial Economics

Subjects
TheoryofComputation_MISCELLANEOUS, R41, Uncertain Demand, R42, Traffic Congestion, H23, Road Pricing, Road Network, ddc:330, Private Supply, D63, Auction
Abstract

There has been wide interest in private supply of roads as a solution to traffic congestion. We study its efficiency under demand uncertainty: we solve for equilibrium and optimum as benchmarks, and evaluate the efficiency of possible regulatory policies for private road operators. We obtain analytic solutions for simple networks and numerical simulation results for more complex ones. For two serial links and two parallel links, self-financing still holds in expected terms for the first-best case, even though the capacity is higher than the capacity for the deterministic demand equal to the expected value. When forced to apply the second-best optimal pricing, the private supplier makes an expected loss (profit) if there is an untolled substitute (complement) in the network. In contrast to the deterministic counterpart of the problem we study, regulation by competitiv e auction cannot replicate the second-best zero-profit result. For more complex networks, when private firms adds capacity one link at a time, entry by competitive auctions performs better than free entry. For the parameter range considered in the numerical simulation, entry by generalized auction performs better than entry by patronage auction.

Published
2015

25. Comparative research on spatial quality in Europe: motivation and approach

Author

Nijkamp, P., Bergh, J. Van Den, and Verhoef, E.

Subjects
Spatial systems -- Environmental aspects, Environmental services industry
Abstract

Byline: P. Nijkamp, J. van den Bergh, E. Verhoef This paper presents the structure of the ESF-founded TERM research project 'Environmental Quality in European Space', and serves as the introduction to the special issue presenting the results of this project. The aim of the project was to organise existing European research teams in the area of spatial sustainability, focusing on two themes 'transport and environment', and 'energy efficiency and spatial sustainability'. A number of criteria are identified for the comparison and evaluation of research in these areas for 12 European countries: UK, Greece, Hungary, Italy, the Netherlands, Finland, Ireland, Sweden, Denmark, Russia, Israel and Austria. These criteria involve: 'intrinsic characteristics' (problem definition, policy options, theoretical assumptions, method and data) and 'meta characteristics' (scientific innovation and contribution to real policy-making).

Published
2003

27. Introduction

Author

Steg, L., Verhoef, E, Bliemer, M, Van Wee, B., Verhoef, E., van Wee, B., Bliemer, M., Social Psychology, and Heymans Institute for Psychological Research

Published
2008

34. Give or take? Rewards vs. Charges for a Congested Bottleneck

Author

Jan Rouwendal, Verhoef, E. T., Knockaert, J., Spatial Economics, and CLUE+

Subjects
R41, Subsidies, Scheduling-Verfahren, R48, Straßenbenutzungsgebühr, Bottleneck, Verkehrsstau, D62, ddc:330, Verkehrssubvention, Bottleneck model, Traffic congestion, Rewards, Road pricing
Abstract

This paper analyzes the possibilities to relieve congestion using rewards instead of taxes, as well as combinations of rewards and taxes. The model considers a Vickrey-ADL model of bottleneck congestion with endogenous scheduling. With inelastic demand, a fine (time-varying) reward is equivalent to a fine toll, and to a continuum of combinations of time-varying tolls and rewards (including fine feebates). When demand is price sensitive, a reward becomes less attractive from the efficiency viewpoint, because it attracts additional users to the congested bottleneck. As a result, both the second-best optimal rate of participation in the scheme, and the relative efficiency that can be achieved with it, decreases when demand becomes more elastic. Our analytical and simulation results for coarse schemes suggest that a coarse reward is less effective than a coarse feebate, which is itself less effective than a coarse toll. The most efficient coarse system is the step toll, which is also allowed to be positive in the shoulder period.

Published
2010

35. Valuation of flood risk in The Netherlands

Author

Bočkarjova, M., Rietveld, P., Verhoef, E. T., Spatial Economics, CLUE+, and Tinbergen Institute

Subjects
SDG 11 - Sustainable Cities and Communities
Abstract

So far no extensive literature exists on the valuation of extreme natural hazards pertaining low frequency and high potential impact. In this paper, we attain to fill this gap with the study of flood risk in the Netherlands by means of a stated preference approach. From the choice experiments in our large-scale questionnaire, we expect to receive the estimates of the value of statistical life in flooding, the valuation of inconvenience from getting an injury in flooding and the valuation of inconvenience from a precautionary evacuation. There are two persistent problems encountered in this research: extremely low yearly probabilities of a flood and of dying in a flood (which might be ignored by the respondents in making trade-offs); and flood protection being 100% public responsibility that might further depress individual risk valuation. In order to overcome these problems in our survey, we provide respondents with extensive visualised probability explanations, such as graphic grid paper and risk ladder, before presenting them with choice experiments.

Published
2009

37. Thessalonians 4:1-8: The Thessalonians should live a holy life

Author

Verhoef, E

Abstract

The author argues that 1 Thessalonians 4:1-8 should be considered as one coherent pericope. It shows that the term “holiest” does not refer to the god “Kabeiros”, neither that the Greek word “skeuos” means either “spouse” or referring to the male sexual organ. It rather means “body”. The article aims to argue that 1 Thessalonians 4:1-8 is a passage in which Paul urges the Thessalonians to be always pure in body and mind. Thus explained, the pericope fits in with the preceding text about the Thessalonians' holiness at the parousia (3:13) and it prepares for the next paragraph in which the parousia of the Lord with the holy people (3:13) is discussed more thoroughly (1 Th 4:13-5:11). HTS Theological Studies Vol. 63 (1) 2007: pp. 347-363

Published
2008

38. The Information Content of a Stated Choice Experiment

Author

Jan Rouwendal, Blaeij, A. T., Rietveld, P., Verhoef, E. T., and Spatial Economics

Subjects
value of a statistical life, R41, Test, Informationswert, Wert des Lebens, Menschen, D61, Diskrete Entscheidung, ddc:330, C81, D12, Bewertung, Niederlande, stated preferences
Abstract

This paper presents a method to assess the distribution of values of time, and values of statistical life, over participants to a stated choice experiment, that does not require the researcher to make an a priori assumption on the type of distribution, as is required for example for mixed logit models. The method requires a few assumptions to hold true, namely that the valuations to be determined are constant for each individual, and that respondents make choices according to their preferences. These assumptions allow the derivation of lower and upper bounds on the (cumulative) distribution of the values of interest over respondents, by deriving for each choice set the value(s) for which the respondent would be indifferent between the alternatives offered, and next deriving from the choice actually made the respondent’s implied minimum or maximum value(s). We also provide an extension of the method that incorporates the possibility that errors are made. The method is illustrated using data from an experiment investigating the value of time and the value of statistical life. We discuss the possibility to improve the information content of stated choice experiments by optimizing the attribute levels shown to respondents, which is especially relevant because it would help in selecting the appropriate distribution for mixed logit estimates for the same data.

Published
2008

39. Choice of season cards in public transport: a study of a SP experiment

Author

Kroes, E. P., Vincent A.C. van den Berg, Verhoef, E. T., and Spatial Economics

Subjects
GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Hardware_REGISTER-TRANSFER-LEVELIMPLEMENTATION, Hardware_LOGICDESIGN
Abstract

http://hdl.handle.net/1871/32362

Published
2008

40. Firms' perception and acceptability of transport pricing

Author

Steg, L., Tillema, T., Van Wee, T., Schuitema, G., Verhoef, E., van Wee, B., Bliemer, M., Social Psychology, Heymans Institute for Psychological Research, Faculty of Spatial Sciences, and Urban and Regional Studies Institute

Published
2008

41. The information content of a stated choice experiment : a new method and its application to the value of a statistical life

Author

Rouwendal, J., de Blaeij, A.T., Rietveld, P., and Verhoef, E.

Subjects
economie m.b.t. consumenten, consumer economics, consumenten, choice behaviour, economics, microeconomics, consumers, micro-economische analyse, Urban Economics, LEI Regionale Economie en Ruimtegebruik, LEI Regional economy & land use, MGS, cost benefit analysis, transport, microeconomic analysis, kosten-batenanalyse, LEI Regionale Economie & Ruimtegebruik, economie, keuzegedrag, micro-economie
Published
2008

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