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14. NRXN1α+/- is associated with increased excitability in ASD iPSC-derived neurons

Author

Avazzadeh, Sahar, Quinlan, Leo R., Reilly, Jamie, McDonagh, Katya, Jalali, Amirhossein, Wang, Yanqin, McInerney, Veronica, Krawczyk, Janusz, Ding, Yicheng, Fitzgerald, Jacqueline, O’Sullivan, Matthew, Forman, Eva B., Lynch, Sally A., Ennis, Sean, Feerick, Niamh, Reilly, Richard, Li, Weidong, Shen, Xu, Yang, Guangming, Lu, Yin, Peeters, Hilde, Dockery, Peter, O’Brien, Timothy, Shen, Sanbing, and Gallagher, Louise

Published
2021
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15. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author

O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Parikshak, Neelroop N, Newhouse, Stephen, Ripke, Stephan, Neale, Benjamin M, Purcell, Shaun M, Posthuma, Danielle, Nurnberger, John I, Lee, S Hong, Faraone, Stephen V, Perlis, Roy H, Mowry, Bryan J, Thapar, Anita, Goddard, Michael E, Witte, John S, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan E, Asherson, Philip, Azevedo, Maria H, Backlund, Lena, Badner, Judith A, Bailey, Anthony J, Banaschewski, Tobias, Barchas, Jack D, Barnes, Michael R, Barrett, Thomas B, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayes, Monica, Bellivier, Frank, Bergen, Sarah E, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B, Black, Donald W, Blackwood, Douglas HR, Bloss, Cinnamon S, Boehnke, Michael, Boomsma, Dorret I, Breuer, Rene, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy G, Buitelaar, Jan K, Bunney, William E, Buxbaum, Joseph D, Byerley, William F, Byrne, Enda M, Caesar, Sian, Cahn, Wiepke, Cantor, Rita M, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Mattheisen, Manuel, Cloninger, C Robert, Collier, David A, Cook, Edwin H, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William H, Craig, David W, Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary J, Doyle, Alysa E, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard P, Edenberg, Howard J, Elia, Josephine, Ennis, Sean, Etain, Bruno, and Fanous, Ayman

Subjects
Human Genome, Brain Disorders, Serious Mental Illness, Schizophrenia, Genetics, Depression, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Brain, Databases, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Histones, Humans, Mental Disorders, Signal Transduction, Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Published
2015

16. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

Author

Pinto, Dalila, Delaby, Elsa, Merico, Daniele, Barbosa, Mafalda, Merikangas, Alison, Klei, Lambertus, Thiruvahindrapuram, Bhooma, Xu, Xiao, Ziman, Robert, Wang, Zhuozhi, Vorstman, Jacob AS, Thompson, Ann, Regan, Regina, Pilorge, Marion, Pellecchia, Giovanna, Pagnamenta, Alistair T, Oliveira, Bárbara, Marshall, Christian R, Magalhaes, Tiago R, Lowe, Jennifer K, Howe, Jennifer L, Griswold, Anthony J, Gilbert, John, Duketis, Eftichia, Dombroski, Beth A, De Jonge, Maretha V, Cuccaro, Michael, Crawford, Emily L, Correia, Catarina T, Conroy, Judith, Conceição, Inês C, Chiocchetti, Andreas G, Casey, Jillian P, Cai, Guiqing, Cabrol, Christelle, Bolshakova, Nadia, Bacchelli, Elena, Anney, Richard, Gallinger, Steven, Cotterchio, Michelle, Casey, Graham, Zwaigenbaum, Lonnie, Wittemeyer, Kerstin, Wing, Kirsty, Wallace, Simon, van Engeland, Herman, Tryfon, Ana, Thomson, Susanne, Soorya, Latha, Rogé, Bernadette, Roberts, Wendy, Poustka, Fritz, Mouga, Susana, Minshew, Nancy, McInnes, L Alison, McGrew, Susan G, Lord, Catherine, Leboyer, Marion, Le Couteur, Ann S, Kolevzon, Alexander, González, Patricia Jiménez, Jacob, Suma, Holt, Richard, Guter, Stephen, Green, Jonathan, Green, Andrew, Gillberg, Christopher, Fernandez, Bridget A, Duque, Frederico, Delorme, Richard, Dawson, Geraldine, Chaste, Pauline, Café, Cátia, Brennan, Sean, Bourgeron, Thomas, Bolton, Patrick F, Bölte, Sven, Bernier, Raphael, Baird, Gillian, Bailey, Anthony J, Anagnostou, Evdokia, Almeida, Joana, Wijsman, Ellen M, Vieland, Veronica J, Vicente, Astrid M, Schellenberg, Gerard D, Pericak-Vance, Margaret, Paterson, Andrew D, Parr, Jeremy R, Oliveira, Guiomar, Nurnberger, John I, Monaco, Anthony P, Maestrini, Elena, Klauck, Sabine M, Hakonarson, Hakon, Haines, Jonathan L, Geschwind, Daniel H, Freitag, Christine M, Folstein, Susan E, and Ennis, Sean

Subjects
Genetics, Brain Disorders, Pediatric, Mental Health, Intellectual and Developmental Disabilities (IDD), Neurosciences, Autism, 2.1 Biological and endogenous factors, Aetiology, Child, Child Development Disorders, Pervasive, DNA Copy Number Variations, Female, Gene Regulatory Networks, Humans, Male, Metabolic Networks and Pathways, Multigene Family, Pedigree, Sequence Deletion, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.

Published
2014

18. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

Author

Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan, Asherson, Philip, Azevedo, Maria, Backlund, Lena, Badner, Judith, Bailey, Anthony, Banaschewski, Tobias, Barchas, Jack, Barnes, Michael, Barrett, Thomas, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayés, Mònica, Bellivier, Frank, Bergen, Sarah, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth, Black, Donald, Blackwood, Douglas, Boehnke, Michael, Boomsma, Dorret, Breen, Gerome, Breuer, René, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy, Buitelaar, Jan, Bunney, William, Buxbaum, Joseph, Byerley, William, Byrne, Enda, Caesar, Sian, Cahn, Wiepke, Cantor, Rita, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Cloninger, C, Collier, David, Cook, Edwin, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William, Craig, David, Craig, Ian, Crosbie, Jennifer, Cuccaro, Michael, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary, Doyle, Alysa, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard, Edenberg, Howard, Elia, Josephine, Ennis, Sean, Etain, Bruno, Fanous, Ayman, Farmer, Anne, Ferrier, I, Flickinger, Matthew, Fombonne, Eric, Foroud, Tatiana, Frank, Josef, Franke, Barbara, Fraser, Christine, Freedman, Robert, Giegling, Ina, Gill, Michael, Gordon, Scott, Gordon-Smith, Katherine, Green, Elaine, Greenwood, Tiffany, Grice, Dorothy, Gross, Magdalena, Grozeva, Detelina, and Guan, Weihua

Subjects
Adult, Attention Deficit Disorder with Hyperactivity, Bipolar Disorder, Child, Child Development Disorders, Pervasive, Crohn Disease, Depressive Disorder, Major, Genetic Heterogeneity, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Inheritance Patterns, Mental Disorders, Polymorphism, Single Nucleotide, Schizophrenia
Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohns disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Published
2013

19. Competition and Price Dispersion in International Long Distance Calling

Author

Ennis, Sean F.

Subjects
Computer Science - Computers and Society, K.4.m Miscellaneous
Abstract

This paper examines the relationship between changes in telecommunications provider concentration on international long distance routes and changes in prices on those routes. Overall, decreased concentration is associated with significantly lower prices to consumers of long distance services. However, the relationship between concentration and price varies according to the type of long distance plan considered. For the international flagship plans frequently selected by more price-conscious consumers of international long distance, increased competition on a route is associated with lower prices. In contrast, for the basic international plans that are the default selection for consumers, increased competition on a route is actually associated with higher prices. Thus, somewhat surprisingly, price dispersion appears to increase as competition increases., Comment: 29th TPRC Conference, 2001

Published
2001

20. The role of rare compound heterozygous events in autism spectrum disorder

Author

Lin, Bochao Danae, Colas, Fabrice, Nijman, Isaac J., Medic, Jelena, Brands, William, Parr, Jeremy R., van Eijk, Kristel R., Klauck, Sabine M., Chiocchetti, Andreas G., Freitag, Christine M., Maestrini, Elena, Bacchelli, Elena, Coon, Hilary, Vicente, Astrid, Oliveira, Guiomar, Pagnamenta, Alistair T., Gallagher, Louise, Ennis, Sean, Anney, Richard, Bourgeron, Thomas, Luykx, Jurjen J., and Vorstman, Jacob

Published
2020
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22. Periventricular Calcification, Abnormal Pterins and Dry Thickened Skin: Expanding the Clinical Spectrum of RMND1?

Author

Casey, Jillian P., Crushell, Ellen, Thompson, Kyle, Twomey, Eilish, He, Langping, Ennis, Sean, Philip, Roy K., Taylor, Robert W., King, Mary D., Lynch, Sally Ann, Baumgartner, Matthias, Series editor, Patterson, Marc, Series editor, Rahman, Shamima, Series editor, Peters, Verena, Series editor, Morava, Eva, Editor-in-chief, and Zschocke, Johannes, Series editor

Published
2016
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24. Increased Ca2+ signaling in NRXN1α+/− neurons derived from ASD induced pluripotent stem cells

Author

Avazzadeh, Sahar, McDonagh, Katya, Reilly, Jamie, Wang, Yanqin, Boomkamp, Stephanie D., McInerney, Veronica, Krawczyk, Janusz, Fitzgerald, Jacqueline, Feerick, Niamh, O’Sullivan, Matthew, Jalali, Amirhossein, Forman, Eva B., Lynch, Sally A., Ennis, Sean, Cosemans, Nele, Peeters, Hilde, Dockery, Peter, O’Brien, Timothy, Quinlan, Leo R., Gallagher, Louise, and Shen, Sanbing

Published
2019
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31. Impact assessment support study for the review of the Community guidelines on State aid for railway undertakings

Author

Gabriel, Margaux, Głowicka, Ela, Hedge, Vedika, Jeschonneck, Malte, Mattes, Anselm, Rancati, Luca, Urzi, Francesca, Dente, Gabriele, Nava, Salvatore, Salomone, Elena, Deller, David, Ennis, Sean F., Enstone, Bryn, Alvarez Vidal, Ana, el-Houda Bey, Nour, Hofmann, Michael, and Klotz, Robert

Abstract

In the wake of stagnant modal share of the European rail freight sector, this support study provides market information for the revision of the Guidelines on State aid for railway undertakings. It addresses four areas of interest: status of rail infrastructure; accessibility and costs pertaining to rolling stock; profitability and demand elasticity of rail freight ser- vices; and effectiveness of State support measures. A novel dataset of costs and revenues of rail freight across Europe, compiled using both publicly available data and input from extensive stakeholder consultation was built for that purpose. The findings are as follows. The inadequacy of intermodal terminals, congested rail networks, and costliness of private sidings all restrict the capacity of European rail infrastructure. Access to rolling stock is characterised by high costs and a lack of technical standardisation across Member States. We find that rail freight sectors in many countries are loss-making, with some segments being profitable. Efficient transshipment and transport of high freight volumes over long distances improves profitability of intermodal operations. The study shows that price sen- sitivity of rail freight services differs depending on the level of competition faced by road transport. The study also highlights to what extent higher thresholds for proportionate State aid and improved flexibility of schemes could be considered.

Published
2023

32. Advantages of Licence-Exempt Spectrum::Allocation Versus Auctions for Upper 6Ghz Spectrum

Author

Ennis, Sean

Abstract

This paper examines the relative advantages of allocating spectrum by auction or without licensing. The debate over how to allocate the spectrum will at times rest fundamentally on the challenges of choosing between alternative technologies. This paper notes that economic benefits of a highly distributed and non-excludable technology, like Wi-Fi, may be higher than for an excludable technology, like mobile data, but that the bidding capacities of each technology can easily sway towards an excludable technology due to a highly distributed technology’s inability to appropriate gains and thus to reflect its underlying social gains in bids. This argument is developed specifically with respect to the upper 6 GHz band of spectrum. The paper argues that reserving this band as unlicensed spectrum would plausibly deliver higher social surplus, higher economic value to government and reduced user costs compared to allocating the band via auction.

Published
2023

33. Price parity clauses for hotel room booking: empirical evidence from regulatory change

Author

Ennis, Sean, Ivaldi, Marc, and Lagos, Vicente

Subjects
TheoryofComputation_GENERAL, B- ECONOMIE ET FINANCE, ComputingMilieux_MISCELLANEOUS
Abstract

This paper examines the impact of most favored nation (MFN) clauses on retail prices, taking advantage of two natural experiments that changed vertical contracting between hotels and major digital platforms. The broad E.U. intervention narrowed the breadth of “price parity” obligations between hotels and major Online Travel Agencies (OTAs). Direct sales by hotels to customers subsequently became relatively cheaper. Comparisons with hotel pricing outside the E.U. confirm the reduction in prices for mid-level and luxury hotels. France and Germany went further and eliminated all price-parity agreements. This stronger intervention was associated solely with a significant additional price-reducing effect for mid-level hotels in Germany. Overall, wide MFNs are associated with higher retail prices. Regulating MFNs reduced prices with primary effects coming either from the narrow price-parity intervention or, perhaps, from direct sales becoming cheaper than OTAs in both E.U. and non-E.U. countries, and, interestingly, not from complete elimination of MFNs.

Published
2023

35. Fully reaping the benefits of recent competition-enhancing reforms

Author

Araújo, Sónia, primary, Blancas, Andrés, additional, Bourassa, Frédéric, additional, Carblanc, Anne, additional, Cervantes, Mario, additional, Ennis, Sean, additional, Flores, Manuel, additional, Gonzales, Frédéric, additional, Gonzalez-Fanfalone, Alexia, additional, Gurpegui, Iratxe, additional, Karttunnen, Marianna, additional, Madrigal, Gloriana, additional, Morales, Guillermo, additional, Paltridge, Sam, additional, Serra-Vallejo, Cristina, additional, Serve, Blandine, additional, Spiezia, Vincenzo, additional, Spinelli, Francesca, additional, and Weber, Verena, additional

Published
2018
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36. Sacar el mejor provecho de las recientes reformas para fortalecer la competencia

Author

Araújo, Sónia, primary, Blancas, Andrés, additional, Bourassa, Frédéric, additional, Carblanc, Anne, additional, Cervantes, Mario, additional, Ennis, Sean, additional, Flores, Manuel, additional, Gonzales, Frédéric, additional, Gonzalez-Fanfalone, Alexia, additional, Gurpegui, Iratxe, additional, Karttunnen, Marianna, additional, Madrigal, Gloriana, additional, Morales, Guillermo, additional, Paltridge, Sam, additional, Serra-Vallejo, Cristina, additional, Serve, Blandine, additional, Spiezia, Vincenzo, additional, Spinelli, Francesca, additional, and Weber, Verena, additional

Published
2018
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39. Energy Data Sharing and The Case of EV Smart Charging

Author

Ennis, Sean and Colangelo, Giuseppe

Abstract

This report examines the potential impacts of data sharing related to electric vehicle battery charging and electricity provision. The report arrives at a moment of regulatory ambiguity in the EU over the nature of data sharing that will be involved in this industry and whether there will be EU rules or national rules that ensure choice and prevent data monopolisation. Resolving the ambiguity is important due to the potentially decisive role that car batteries can ultimately play in storing variable renewable energy, like wind and solar, and returning this energy to the network at times of high demand. We maintain that the main regulatory challenges are represented by the policy choices related to interoperability and standardisation, in particular the option for a mandated rather than a facilitated API adoption, and the concerns about privacy and cybersecurity. Failure to require openness at an early stage is not likely to be counteracted by high customer demand for openness and could create lock-in for car customers to “mini” monopolies. Openness does not require imposition of one standard: openness only implies open access to each standard and information held

Published
2022

40. The Cost Escalation of Rail Projects: Using Previous Experience to Re-Evaluate the CalSpeed Estimates

Author

Leavitt, Dan, Ennis, Sean, and McGovern, Pat

Abstract

This report is a follow-up study to last year's CalSpeed publication, "High-Speed Trains for California," Working Paper No. 565. The purpose of this paper is to test rigorously and critically the cost estimate methodology presented in that previous working paper. This has been accomplished primarily by focusing on the issue of cost escalation of rail projects, with reference to both U.S. and foreign experience.

Published
1993

41. Consumer Expectations and Fair Contracting for Digital Products

Author

Ennis, Sean

Abstract

The formation of consumer expectations for digital products affects competition between digital platforms that offer competing products. Unfair competition may occur if the competitive outcome is influenced my misled expectations, notably if the company that wins the competition either misled consumers or did not affirmatively correct consumer expectations that were incorrect. The ability to exploit customers whose expectations have been misled is particularly strong for networks that have tipped, as outside alternatives for dissatisfied consumers may no longer be realistic or viable alternatives for consumers. Unilateral deviations by a company’s product away from the future product expectations that have been created around their products may be unfair and create anti-competitive outcomes in growing digital markets.

Published
2022

44. Multiple-Choice Question Tests: A Convenient, Flexible and Effective Learning Tool? A Case Study

Author

Douglas, Mercedes, Wilson, Juliette, and Ennis, Sean

Abstract

The research presented in this paper is part of a project investigating assessment practices, funded by the Scottish Funding Council. Using established principles of good assessment and feedback, the use of online formative and summative multiple choice tests (MCT's) was piloted to support independent and self-directed learning and improve performance in an efficient manner for both students and staff. The paper reviews previous studies that have examined the relevance of MCT's and presents an evaluation of the students grades and the results of a questionnaire designed to capture their perceptions about the effectiveness of MCT's. Our findings identify improvements on students' marks and positive responses from students who found MCT's to be useful at supporting their learning of basic concepts and building confidence and self-esteem. We also argue that MCT's work more effectively when used in conjunction with other assessment methods. (Contains 2 tables and 2 figures.)

Published
2012
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46. Sector Inquiry:Definition and Commentary

Author

Ennis, Sean

Abstract

"Sector inquiries" as performed by competition authorities are focused on first, identifying regulatory, behavioural or structural problems in a market that can explain perceived failures of competition and second, suggesting solutions for improving competitive outcomes or processes. This note focuses on sector inquiries (or market studies), in the context of competition.

Published
2022

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