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1. Analysis of shared heritability in common disorders of the brain

Author

Anttila, V., Bulik-Sullivan, B., Finucane, H.K., Walters, R.K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G.J., Gormley, P., Malik, R., Patsopoulos, N.A., Ripke, S., Wei, Z., Yu, D., Lee, P.H., Turley, P., Grenier-Boley, B., Chouraki, V., Kamatani, Y., Berr, C., Letenneur, L., Hannequin, D., Amouyel, P., Boland, A., Deleuze, J.F., Duron, E., Vardarajan, B.N., Reitz, C., Goate, A.M., Huentelman, M.J., Kamboh, M.I., Larson, E.B., Rogaeva, E., George-Hyslop, P. St, Hakonarson, H., Kukull, W.A., Farrer, L.A., Barnes, L.L., Beach, T.G., Demirci, F.Y., Head, E., Hulette, C.M., Jicha, G.A., Kauwe, J.S.K., Kaye, J.A., Leverenz, J.B., Levey, A.I., Lieberman, A.P., Pankratz, V.S., Poon, W.W., Quinn, J.F., Saykin, A.J., Schneider, L.S., Smith, A.G., Sonnen, J.A., Stern, R.A., Deerlin, V.M. Van, Eldik, L.J. Van, Harold, D., Russo, G., Rubinsztein, D.C., Bayer, A., Tsolaki, M., Proitsi, P., Fox, N.C., Hampel, H., Owen, M.J., Mead, S., Passmore, P., Morgan, K., Nothen, M.M., Rossor, M., Lupton, M.K., Hoffmann, P., Kornhuber, J., Lawlor, B., McQuillin, A., Al-Chalabi, A., Bis, J.C., Ruiz, A., Boada, M., Seshadri, S., Beiser, A., Rice, K., Lee, S.J. van der, Jager, P.L. De, Geschwind, D.H., Riemenschneider, M., Riedel-Heller, S., Rotter, J.I., Ransmayr, G., Hyman, B.T., Cruchaga, C., Alegret, M., Winsvold, B., Palta, P., Farh, K.H., Cuenca-Leon, E., Furlotte, N., Kurth, T., et al., Stroink, H., Franke, B., Buitelaar, J.K., Arias Vasquez, A., Corvin, A., and Neale, B.M.

Subjects
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Abstract

Contains fulltext : 193271pub.pdf (Publisher’s version ) (Open Access) Contains fulltext : 193271pre.pdf (Author’s version preprint ) (Open Access) Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. 13 p.

Published
2018
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2. ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties

Author

St Pourcain, B., Robinson, E., Anttila, V., Sullivan, B., Maller, J, Golding, J, Skuse, D, Ring, S., Evans, D M, Zammit, S, Fisher, S.E., Neale, B., Anney, R J L, Ripke, S., Hollegaard, M V, Werge, T., iPSYCH-SSI-Broad Autism Group, ., Ronald, A., Grove, J, Hougaard, D M, Børglum, A.D., Mortensen, P B, Daly, M J, and Davey Smith, G.

Subjects
Neuroinformatics, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Contains fulltext : 181483.pdf (Publisher’s version ) (Open Access) 03 januari 2017 8 p.

Published
2017

3. Correction: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

Author

Gormley, P, Anttila, V, Winsvold, BS, Palta, P, Esko, T, Pers, TH, Farh, KH, Cuenca-Leon, E, Muona, M, Furlotte, NA, Kurth, T, Ingason, A, McMahon, G, Ligthart, L, Terwindt, GM, Kallela, M, Freilinger, TM, Ran, C, Gordon, SG, Stam, AH, Steinberg, S, Borck, G, Koiranen, M, Quaye, L, Adams, HHH, Lehtimäki, T, Sarin, AP, Wedenoja, J, Hinds, DA, Buring, JE, Schürks, M, Ridker, PM, Gudlaug Hrafnsdottir, M, Stefansson, H, Ring, SM, Hottenga, JJ, Penninx, BWJH, Färkkilä, M, Artto, V, Kaunisto, M, Vepsäläinen, S, Malik, R, Heath, AC, Madden, PAF, Martin, NG, Montgomery, GW, Kurki, MI, Kals, M, Mägi, R, Pärn, K, Hämäläinen, E, Huang, H, Byrnes, AE, Franke, L, Huang, J, Stergiakouli, E, Lee, PH, Sandor, C, Webber, C, Cader, Z, Muller-Myhsok, B, Schreiber, S, Meitinger, T, Eriksson, JG, Salomaa, V, Heikkilä, K, Loehrer, E, Uitterlinden, AG, Hofman, A, Van Duijn, CM, Cherkas, L, Pedersen, LM, Stubhaug, A, Nielsen, CS, Männikkö, M, Mihailov, E, Milani, L, Göbel, H, Esserlind, AL, Francke Christensen, A, Folkmann Hansen, T, Werge, T, Kaprio, J, Aromaa, AJ, Raitakari, O, Arfan Ikram, M, Spector, T, Järvelin, MR, Metspalu, A, Kubisch, C, Strachan, DP, Ferrari, MD, Belin, AC, Dichgans, M, Wessman, M, Van den Maagdenberg, AMJM, Zwart, JA, Boomsma, DI, and Davey Smith, G

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology
Abstract

In the version of this article initially published online, the affiliations for Bertram Muller-Myhsok and Patricia Pozo-Rosich were incorrect or incomplete. These errors have been corrected for the print, PDF and HTML versions of this article.

Published
2016

4. IFITM3 restricts the morbidity and mortality associated with influenza

Author

Everitt, A, Clare, S, Pertel, T, John, S, Wash, R, Smith, SE, Chin, C, Feeley, E, Sims, J, Adams, D, Wise, H, Kane, L, Goulding, D, Digard, P, Anttila, V, Baillie, J, Walsh, T, Hume, D, Palotie, A, Xue, Y, Colonna, V, Tyler-Smith, C, Dunning, J, Gordon, S, and Everingham, K

Published
2016

5. Integrating common and rare genetic variation in diverse human populations

Author

Altshuler, D, Gibbs, R, Peltonen, L, Dermitzakis, E, Schaffner, S, Yu, F, Bonnen, P, de Bakker, P, Deloukas, P, Gabriel, S, Gwilliam, R, Hunt, S, Inouye, M, Jia, X, Palotie, A, Parkin, M, Whittaker, P, Chang, K, Hawes, A, Lewis, L, Ren, Y, Wheeler, D, Muzny, D, Barnes, C, Darvishi, K, Hurles, M, Korn, J, Kristiansson, K, Lee, C, McCarrol, SA, Nemesh, J, Keinan, A, Montgomery, S, Pollack, S, Price, A, Soranzo, N, Gonzaga-Jauregui, C, Anttila, V, Brodeur, W, Daly, M, Leslie, S, McVean, G, Moutsianas, L, Nguyen, H, Zhang, Q, Ghori, M, McGinnis, R, McLaren, W, Takeuchi, F, Grossman, SR, Shlyakhter, I, Hostetter, E, Sabeti, P, Adebamowo, C, Foster, M, Gordon, DR, Licinio, J, Manca, M, Marshall, P, Matsuda, I, Ngare, D, Wang, V, Reddy, D, Rotimi, C, Royal, C, Sharp, R, Zeng, C, Brooks, L, McEwen, J, Dermitzakis, Emmanouil, and Montgomery, Stephen

Subjects
DNA Copy Number Variations, Single-nucleotide polymorphism, Genome-wide association study, Human genetic variation, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Genome, Human, 0302 clinical medicine, Population Groups, Population Groups/*genetics, Human Genome Project, Humans, ddc:576.5, Copy-number variation, International HapMap Project, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, SNP genotyping, Minor allele frequency, 030217 neurology & neurosurgery, Imputation (genetics)
Abstract

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of

Published
2010
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6. Decompressive hemicraniectomy for treatment of space occupying ischemic stroke after repair of type-A aortic dissection

Author

Biancari, F., Lahtinen, M., Erkinaro, T., Janne Liisanantti, Anttila, V., and D Andrea, V.

Subjects
hemicraniectomy, Male, Stroke, Decompressive Craniectomy, cardiovascular surgery, Aortic Aneurysm, Thoracic, Aortic, Humans, Aortic, cardiovascular surgery, hemicraniectomy, stroke
Abstract

Postoperative stroke after cardiac surgery is often a lethal complication. Herein, we report on a patient who suffered space-occupying ischemic stroke after surgical treatment of type A aortic dissection. He underwent decompressive hemicraniectomy and, despite residual hemianopsia and left side flaccid hemiplegia, survived surgery and was discharged for rehabilitation. This observation suggests that early consultation with a neurosurgeon, intracranial pressure monitoring and, when indicated, decompressive hemicraniectomy should be considered in order to reduce the high mortality rate associated with ischemic stroke after cardiac surgery.

Published
2015

7. Migraine without aura: genome-wide association analysis identifies several novel susceptibility

Author

de Vries B, Freilinger T, Anttila V, Malik R, Kallela M, Gm, Terwindt, Pozo-Rosich P, Winsvold B, Dr, Nyholt, Wp, Oosterhout, Artto V, Todt U, Hämäläinen E, Fernández-Morales J, Ma, Louter, Ma, Kaunisto, Schoenen J, Raitakari O, Lehtimäki T, Vila-Pueyo M, Göbel H, Wichmann E, Sintas C, Ag, Uitterlinden, Hofman A, Rivadeneira F, Heinze A, Tronvik E, Cm, Duijn, Kaprio J, Bru Cormand, Wessman M, Rr, Frants, Meitinger T, Müller-Myhsok B, Zwart J, Färkkilä M, Macaya A, Md, Ferrari, Kubisch C, Palotie A, Dichgans M, and Am, Den Maagdenberg

Subjects
medicine.medical_specialty, Neurology, endocrine system diseases, Aura, business.industry, Pain medicine, Clinical Neurology, Genome-wide association study, General Medicine, Bioinformatics, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Migraine, Poster Presentation, medicine, Genome-Wide Association Analysis, Genetic predisposition, 030212 general & internal medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, Genetic association
Abstract

Genome-wide association studies (GWAS) are a novel and promising method to study genetic susceptibility factors for common disorders, including migraine.

Published
2013
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8. IFITM3 restricts the morbidity and mortality associated with influenza

Author

Everitt, AR, Clare, S, Pertel, T, John, SP, Wash, RS, Smith, SE, Chin, CR, Feeley, EM, Sims, JS, Adams, DJ, Wise, HM, Kane, L, Goulding, D, Digard, P, Anttila, V, Baillie, JK, Walsh, TS, Hume, DA, Palotie, A, Xue, Y, Colonna, V, Tyler-Smith, C, Dunning, J, Gordon, SB, Everingham, K, Dawson, H, Hope, D, Ramsay, P, Walsh Local Lead Investigator, TS, Campbell, A, Kerr, S, Harrison, D, Rowan, K, Addison, J, Donald, N, Galt, S, Noble, D, Taylor, J, Webster Local Lead Investigator, N, Taylor Local Lead Investigator, I, Aldridge Local Lead Investigator, J, Dornan, R, Richard, C, Gilmour, D, Simmons Local Lead Investigator, R, White Local Lead Investigator, R, Jardine, C, Williams Local Lead Investigator, D, Booth Local Lead Investigator, M, Quasim, T, Watson, V, Henry, P, Munro, F, Bell, L, Ruddy Local Lead Investigator, J, Cole Local Lead Investigator, S, Southward, J, Allcoat, P, Gray, S, McDougall Local Lead Investigator, M, Matheson, J, Whiteside Local Lead Investigator, J, Alcorn, D, Rooney Local Lead Investigator, K, Sundaram, R, Imrie Local Lead Investigator, G, Bruce, J, McGuigan, K, Moultrie Local Lead Investigator, S, Cairns Local Lead Investigator, C, Grant, J, Hughes, M, Murdoch Local Lead Investigator, C, Davidson Local Lead Investigator, A, Harris, G, Paterson, R, Wallis Local Lead Investigator, C, Binning Local Lead Investigator, S, Pollock, M, Antonelli, J, Duncan, A, Gibson, J, McCulloch, C, Murphy, L, Haley, C, Faulkner, G, Freeman, T, Baillie Principal Investigator, JK, Chaussabel, D, Adamson, WE, Carman, WF, Thompson, C, Zambon, MC, Aylin, P, Ashby, D, Barclay, WS, Brett, SJ, Cookson, WO, Drumright, LN, Elderfield, RA, Garcia-Alvarez, L, Gazzard, BG, Griffiths, MJ, Habibi, MS, Hansel, TT, Herberg, JA, Holmes, AH, Hussell, T, Johnston, SL, Kon, OM, Levin, M, Moffatt, MF, Nadel, S, Openshaw, PJ, Warner, JO, Aston, SJ, Hay, A, McCauley, J, O'Garra, A, Banchereau, J, Hayward, A, Kellam, P, Simmonds, P, McNamara, PS, Semple, MG, Smyth, RL, Nguyen-Van-Tam, JS, Ho, L-P, Mcmichael, AJ, Dougan, G, and Brass, AL

Published
2012

9. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

Author

Anttila, V., Stefansson, H., Kallela, M., Todt, U., Terwindt, G.M., Calafato, M.S., Nyholt, D.R., Dimas, A.S., Freilinger, T., Muller-Myhsok, B., Artto, V., Inouye, M., Alakurtti, K., Kaunisto, M.A., Hamalainen, E., Vries, B. de, Stam, A.H., Weller, C.M., Heinze, A., Heinze-Kuhn, K., Goebel, I., Borck, G., Gobel, H., Steinberg, S., Wolf, C., Bjornsson, A., Gudmundsson, G., Kirchmann, M., Hauge, A., Werge, T., Schoenen, J., Eriksson, J.G., Hagen, K., Stovner, L., Wichmann, E., Meitinger, T., Alexander, M., Moebus, S., Schreiber, S., Aulchenko, Y.S., Breteler, M.M.B., Uitterlinden, A.G., Hofman, A., Duijn, C.M. van, Tikka-Kleemola, P., Lucae, S., Tozzi, F., Muglia, P., Barrett, J., Kaprio, J., Farkkila, M., Peltonen, L., Stefansson, K., Zwart, J.A., Ferrari, M.D., Olesen, J., Daly, M., Wessman, M., Maagdenberg, A.M.J.M. van den, Dichgans, M., Kubisch, C., Dermitzakis, E.T., Frants, R.R., Palotie, A., Vepsalainen, Int Headache Genetics Consortium, Epidemiology, and Internal Medicine

Subjects
Oncology, Glutamate Carboxypeptidase II, Male, medicine.medical_specialty, Genotype, Migraine Disorders, Quantitative Trait Loci, Medizin, Genome-wide association study, Biology, familial hemiplegic migraine lymphoblastoid cell-lines gene-expression episodic ataxia spreading depression confers risk mutation type-2 involvement mechanisms, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Lymphocytes, Familial hemiplegic migraine, Cells, Cultured, 030304 developmental biology, Episodic ataxia, 0303 health sciences, Genome, Human, Calcium-Binding Proteins, Membrane Proteins, RNA-Binding Proteins, MTDH, Odds ratio, medicine.disease, 3. Good health, Minor allele frequency, Migraine, Case-Control Studies, Immunology, Antigens, Surface, Female, Cell Adhesion Molecules, 030217 neurology & neurosurgery, Chromosomes, Human, Pair 8, Genome-Wide Association Study, Microsatellite Repeats
Abstract

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 x 10(-)(9), odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 x 10(-)(1)(1) (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 x 10(-)(5), permuted threshold for genome-wide significance 7.7 x 10(-)(5). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.

Published
2010

10. HMI and Safety-Related Driver Performance

Author

Östlund, J., Nilsson, L., Carsten, O., Merat, N., Jamson, H., Jamson, S., Mouta, S., Carvalhais, J., Santos, J, Anttila, V., Sandberg, H., Luoma, J., Waard, D. de, Brookhuis, K., Johansson, E., Engström, J., Victor, T., Harbluk, J., Janssen, W., Brouwer, R., and Institute for transport studies

Subjects
traffic safety, in-vehicle information systems, human-computer interaction, man-machine interface, Traffic, driver behaviour
Abstract

The aim of HASTE is to develop methodologies and guidelines for the assessment of In-Vehicle Information Systems (IVIS). The intention is to devise an assessment regime that is independent of the design of an IVIS and that is based on an evaluation of driving performance while using the system as compared with driving performance when not using the system (baseline driving). The ambition is to provide an assessment regime which: • Is technology-independent; • Has safety-related criteria; • Is cost effective; • Is appropriate for any system design; and • Is validated through real-world testing. The objective of the experiments in this Workpackage (WP2) was to investigate the impact of IVIS task load on driving performance and safety. To achieve this, two surrogate IVISs (SIVISs) were created, one representing cognitive load and the other visual load. Using these SIVISs, it was possible to vary secondary task load systematically. Separate assessments of the effects on driving of the different types of task load were carried out, with as clean a distinction as possible between visual and cognitive load. The objective was also to identify the advantages and disadvantages of the different assessment methods (laboratory, simulator, field), and finally to identify which road types and scenarios are the most productive for testing IVIS. Different groups of drivers were used and scenarios varied in accordance with the protocol and procedure for safety assessment of IVIS as outlined in Deliverable 1 (Roskam et al., 2002). A very large set of experiments was conducted. But in one sense this was one very large multi-national unified and integrated experiment with a common goal, a common experimental protocol and common indicators. The effect of IVIS use in three distinct road categories — urban, rural, and motorway — was investigated. To do this, a total of 14 separate driving simulator experiments were conducted, with each participant experiencing only one type of S-IVIS. All seven driving simulators were used to investigate driving with both S-IVISs on a common rural road. For the most part, each simulator road type had three levels of difficultly with the most difficult being driving when some critical event was triggered (the motorway had only two levels of difficulty: without and with events).

Published
2004

11. The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort

Author

Eb, Robinson, Kirby A, Ruparel K, Yang J, Lauren McGrath, Anttila V, Bm, Neale, Merikangas K, Lehner T, Pm, Sleiman, Mj, Daly, Gur R, and Hakonarson H

Subjects
Male, Adolescent, Genotype, Developmental Disabilities, Genomics, Neuropsychological Tests, Pediatrics, Polymorphism, Single Nucleotide, Genetic correlation, Community Health Planning, Article, Developmental psychology, Cohort Studies, Heritability, Young Adult, Cellular and Molecular Neuroscience, Cognition, Genetics, Humans, Genetic Predisposition to Disease, Child, Molecular Biology, Philadelphia, Principal Component Analysis, GCTA, Genetic architecture, Cognitive test, Psychiatry and Mental health, Phenotype, Trait, Female, Verbal memory, Cognition Disorders, Psychology
Abstract

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample comprising those aged 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (for example, reading ability, h(2)g=0.43, P=4e-06; emotion identification, h(2)g=0.36, P=1e-05; verbal memory, h(2)g=0.24, P=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (for example, language reasoning and spatial reasoning, r(g)=0.72, P=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities.

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