Percorrer por autor "Duque, Frederico"
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- Analysis of shared heritability in common disorders of the brainPublication . Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K.; Walters, Raymond K.; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J.; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A.; Schoch, Susanne; Sisodiya, Sanjay M.; Smith, Philip; Sperling, Michael; Striano, Pasquale; Surges, Rainer; Thomas, G. Neil; Visscher, Frank; Whelan, Christopher D.; Berr, Claudine; Kurth, Tobias; Zara, Federico; Heinzen, Erin L.; Marson, Anthony; Becker, Felicitas; Stroink, Hans; Zimprich, Fritz; Gasser, Thomas; Gibbs, Raphael; Heutink, Peter; Martinez, Maria; Ligthart, Lannie; Letenneur, Luc; Morris, Huw R.; Sharma, Manu; Ryten, Mina; Mok, Kin Y.; Pulit, Sara; Bevan, Steve; Holliday, Elizabeth; Attia, John; Battey, Thomas; Terwindt, Gisela M.; Boncoraglio, Giorgio; Hannequin, Didier; Thijs, Vincent; Chen, Wei-Min; Mitchell, Braxton; Rothwell, Peter; Sharma, Pankaj; Sudlow, Cathie; Vicente, Astrid; Markus, Hugh; Freilinger, Tobias; Kourkoulis, Christina; Pera, Joana; Amouyel, Philippe; Raffeld, Miriam; Silliman, Scott; Boraska Perica, Vesna; Thornton, Laura M.; Huckins, Laura M.; William Rayner, N.; Lewis, Cathryn M.; Ran, Caroline; Gratacos, Monica; Rybakowski, Filip; Keski-Rahkonen, Anna; Boland, Anne; Raevuori, Anu; Hudson, James I.; Reichborn-Kjennerud, Ted; Monteleone, Palmiero; Karwautz, Andreas; Mannik, Katrin; Gordon, Scott D.; Baker, Jessica H.; O’Toole, Julie K.; Trace, Sara E.; Davis, Oliver S. P.; Deleuze, Jean-François; Helder, Sietske G.; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Danner, Unna N.; van Elburg, Annemarie A.; Borck, Guntram; Clementi, Maurizio; Forzan, Monica; Docampo, Elisa; Lissowska, Jolanta; Hauser, Joanna; Duron, Emmanuelle; Tortorella, Alfonso; Maj, Mario; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Adams, Hieab H.H.; Papezova, Hana; Yilmaz, Zeynep; Wagner, Gudrun; Cohen-Woods, Sarah; Herms, Stefan; Julià, Antonio; Vardarajan, Badri N.; Rabionet, Raquel; Dick, Danielle M.; Ripatti, Samuli; Lehtimäki, Terho; Andreassen, Ole A.; Espeseth, Thomas; Lundervold, Astri J.; Steen, Vidar M.; Pinto, Dalila; Scherer, Stephen W.; Aschauer, Harald; Reitz, Christiane; Schosser, Alexandra; Alfredsson, Lars; Wedenoja, Juho; Padyukov, Leonid; Halmi, Katherine A.; Mitchell, James; Strober, Michael; Bergen, Andrew W.; Kaye, Walter; Szatkiewicz, Jin Peng; Cormand, Bru; Goate, Alison M.; Ramos-Quiroga, Josep Antoni; Ripke, Stephan; Sánchez-Mora, Cristina; Ribasés, Marta; Casas, Miguel; Hervas, Amaia; Arranz, Maria Jesús; Haavik, Jan; Zayats, Tetyana; Johansson, Stefan; Williams, Nigel; Huentelman, Matthew J.; Buring, Julie E.; Elia, Josephine; Dempfle, Astrid; Rothenberger, Aribert; Kuntsi, Jonna; Oades, Robert D.; Banaschewski, Tobias; Franke, Barbara; Buitelaar, Jan K.; Arias Vasquez, Alejandro; Doyle, Alysa E.; Schürks, Markus; Kamboh, M. Ilyas; Reif, Andreas; Lesch, Klaus-Peter; Freitag, Christine; Rivero, Olga; Palmason, Haukur; Romanos, Marcel; Langley, Kate; Rietschel, Marcella; Witt, Stephanie H.; Hrafnsdottir, Maria; Dalsgaard, Soeren; Larson, Eric B.; Børglum, Anders D.; Waldman, Irwin; Wilmot, Beth; Molly, Nikolas; Bau, Claiton H.D.; Crosbie, Jennifer; Schachar, Russell; Loo, Sandra K.; Hottenga, Jouke-Jan; McGough, James J.; Grevet, Eugenio H.; Rogaeva, Ekaterina; Medland, Sarah E.; Robinson, Elise; Weiss, Lauren A.; Bacchelli, Elena; Bailey, Anthony; Bal, Vanessa; Battaglia, Agatino; Penninx, Brenda; Betancur, Catalina; Bolton, Patrick; Cantor, Rita; St George-Hyslop, Peter; Celestino-Soper, Patrícia; Dawson, Geraldine; De Rubeis, Silvia; Duque, Frederico; Green, Andrew; Klauck, Sabine M.; Artto, Ville; Leboyer, Marion; Levitt, Pat; Maestrini, Elena; Mane, Shrikant; Hakonarson, Hakon; De-Luca, Daniel Moreno-; Parr, Jeremy; Regan, Regina; Reichenberg, Abraham; Sandin, Sven; Kaunisto, Mari; Vorstman, Jacob; Wassink, Thomas; Wijsman, Ellen; Cook, Edwin; Santangelo, Susan; Kukull, Walter A.; Delorme, Richard; Rogé, Bernadette; Magalhaes, Tiago; Arking, Dan; Vepsäläinen, Salli; Schulze, Thomas G.; Thompson, Robert C.; Strohmaier, Jana; Matthews, Keith; Melle, Ingrid; Morris, Derek; Farrer, Lindsay A.; Blackwood, Douglas; McIntosh, Andrew; Bergen, Sarah E; Martin, Nicholas G.; Schalling, Martin; Jamain, Stéphane; Maaser, Anna; Fischer, Sascha B.; Reinbold, Céline S.; Fullerton, Janice M.; Grigoroiu-Serbanescu, Maria; Barnes, Lisa L.; Guzman-Parra, José; Mayoral, Fermin; Montgomery, Grant W.; Schofield, Peter R.; Cichon, Sven; Mühleisen, Thomas W.; Degenhardt, Franziska; Schumacher, Johannes; Bauer, Michael; Mitchell, Philip B.; Gershon, Elliot S.; Beach, Thomas G.; Rice, John; Wei, Zhi; Potash, James B.; Zandi, Peter P.; Craddock, Nick; Ferrier, I. Nicol; Alda, Martin; Rouleau, Guy A.; Turecki, Gustavo; Ophoff, Roel; Pato, Carlos; Demirci, F. Yesim; Kurki, Mitja I.; Anjorin, Adebayo; Stahl, Eli; Leber, Markus; Czerski, Piotr M.; Edenberg, Howard J.; Cruceanu, Cristiana; Jones, Ian R.; Posthuma, Danielle; Andlauer, Till F.M.; Forstner, Andreas J.; Hämäläinen, Eija; Head, Elizabeth; Streit, Fabian; Baune, Bernhard T.; Air, Tracy; Sinnamon, Grant; Wray, Naomi R.; MacIntyre, Donald J.; Porteous, David; Homuth, Georg; Rivera, Margarita; Huang, Hailiang; Grove, Jakob; Hulette, Christine M.; Middeldorp, Christel M.; Hickie, Ian; Pergadia, Michele; Mehta, Divya; Smit, Johannes H.; Jansen, Rick; de Geus, Eco; Dunn, Erin; Huang, Jie; Li, Qingqin S.; Nauck, Matthias; Jicha, Gregory A.; Schoevers, Robert A.; Beekman, Aartjan TF; Knowles, James A.; Viktorin, Alexander; Arnold, Paul; Barr, Cathy L.; Bedoya-Berrio, Gabriel; Sandor, Cynthia; Bienvenu, O. Joseph; Brentani, Helena; Burton, Christie; Kauwe, John S.K.; Camarena, Beatriz; Cappi, Carolina; Cath, Danielle; Cavallini, Maria; Cusi, Daniele; Darrow, Sabrina; Webber, Caleb; Denys, Damiaan; Derks, Eske M.; Dietrich, Andrea; Fernandez, Thomas; Kaye, Jeffrey A.; Figee, Martijn; Freimer, Nelson; Gerber, Gloria; Grados, Marco; Greenberg, Erica; Muller-Myhsok, Bertram; Hanna, Gregory L.; Hartmann, Andreas; Hirschtritt, Matthew E.; Hoekstra, Pieter J.; Huang, Alden; Leverenz, James B.; Huyser, Chaim; Illmann, Cornelia; Jenike, Michael; Kuperman, Samuel; Schreiber, Stefan; Leventhal, Bennett; Lochner, Christine; Lyon, Gholson J.; Macciardi, Fabio; Madruga-Garrido, Marcos; Malaty, Irene A.; Levey, Allan I.; Maras, Athanasios; McGrath, Lauren; Miguel, Eurípedes C.; Salomaa, Veikko; Mir, Pablo; Nestadt, Gerald; Nicolini, Humberto; Okun, Michael S.; Pakstis, Andrew; Paschou, Peristera; Piacentini, John; Lieberman, Andrew P.; Pittenger, Christopher; Plessen, Kerstin; Loehrer, Elizabeth; Ramensky, Vasily; Ramos, Eliana M.; Reus, Victor; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Roessner, Veit; Rosário, Maria; Pankratz, Vernon S.; Samuels, Jack F.; Yu, Dongmei; Sandor, Paul; Stein, Dan J.; Tsetsos, Fotis; Van Nieuwerburgh, Filip; Weatherall, Sarah; Wendland, Jens R.; Wolanczyk, Tomasz; Worbe, Yulia; Zai, Gwyneth; Poon, Wayne W.; Göbel, Hartmut; Goes, Fernando S.; McLaughlin, Nicole; Nestadt, Paul S.; Grabe, Hans-Jorgen; Depienne, Christel; Konkashbaev, Anuar; Lanzagorta, Nuria; Valencia-Duarte, Ana; Bramon, Elvira; Buccola, Nancy; Macaya, Alfons; Quinn, Joseph F.; Cahn, Wiepke; Cairns, Murray; Chong, Siow A.; Cohen, David; Crespo-Facorro, Benedicto; Crowley, James; Davidson, Michael; DeLisi, Lynn; Dinan, Timothy; Pozo-Rosich, Patricia; Donohoe, Gary; Saykin, Andrew J.; Drapeau, Elodie; Duan, Jubao; Haan, Lieuwe; Hougaard, David; Karachanak-Yankova, Sena; Khrunin, Andrey; Klovins, Janis; Kučinskas, Vaidutis; Hansen, Thomas; Lee Chee Keong, Jimmy; Limborska, Svetlana; Schneider, Lon S.; Loughland, Carmel; Lönnqvist, Jouko; Maher, Brion; Mattheisen, Manuel; McDonald, Colm; Murphy, Kieran C.; Murray, Robin; Werge, Thomas; Nenadic, Igor; van Os, Jim; Pantelis, Christos; Smith, Amanda G.; Pato, Michele; Petryshen, Tracey; Quested, Digby; Roussos, Panos; Sanders, Alan R.; Schall, Ulrich; Kaprio, Jaakko; Schwab, Sibylle G.; Sim, Kang; So, Hon-Cheong; Stögmann, Elisabeth; Sonnen, Joshua A.; Subramaniam, Mythily; Toncheva, Draga; Waddington, John; Walters, James; Weiser, Mark; Metspalu, Andres; Cheng, Wei; Cloninger, Robert; Curtis, David; Gejman, Pablo V.; Henskens, Frans; Stern, Robert A.; Mattingsdal, Morten; Oh, Sang-Yun; Scott, Rodney; Webb, Bradley; Kubisch, Christian; Breen, Gerome; Churchhouse, Claire; Bulik, Cynthia M.; Daly, Mark; Dichgans, Martin; Faraone, Stephen V.; Van Deerlin, Vivianna M.; Guerreiro, Rita; Holmans, Peter; Kendler, Kenneth S.; Ferrari, Michel D.; Koeleman, Bobby; Mathews, Carol A.; Price, Alkes; Scharf, Jeremiah; Sklar, Pamela; Williams, Julie; Wood, Nicholas W.; Van Eldik, Linda J.; Cotsapas, Chris; Palotie, Aarno; Belin, Andrea C.; Smoller, Jordan W.; Sullivan, Patrick; Rosand, Jonathan; Corvin, Aiden; Neale, Benjamin M.; The Brainstorm Consortium; Harold, Denise; Russo, Giancarlo; Rubinsztein, David C.; Bayer, Anthony; Lee, Phil H.; Tsolaki, Magda; Proitsi, Petra; Fox, Nick C.; Hampel, Harald; Owen, Michael J.; Mead, Simon; Passmore, Peter; Morgan, Kevin; Nöthen, Markus M.; Schott, Jonathan M.; van den Maagdenberg, Arn M.J.M.; Rossor, Martin; Lupton, Michelle K.; Hoffmann, Per; Kornhuber, Johannes; Lawlor, Brian; McQuillin, Andrew; Al-Chalabi, Ammar; Bis, Joshua C; Ruiz, Agustin; Boada, Mercè; Zwart, John-Anker; Seshadri, Sudha; Beiser, Alexa; Rice, Kenneth; van der Lee, Sven J.; De Jager, Philip L.; Geschwind, Daniel H.; Riemenschneider, Matthias; Riedel-Heller, Steffi; Rotter, Jerome I; Ransmayr, Gerhard; Boomsma, Dorret; Hyman, Bradley T.; Cruchaga, Carlos; Alegret, Montserrat; Winsvold, Bendik; Palta, Priit; Farh, Kai-How; Cuenca-Leon, Ester; Furlotte, Nicholas; Eriksson, Nicholas; Olesen, Jes; Chasman, Daniel I.; Nyholt, Dale R.; Anney, Richard; Avbersek, Andreja; Baum, Larry; Turley, Patrick; Berkovic, Samuel; Bradfield, Jonathan; Buono, Russell; Catarino, Claudia B.; Cossette, Patrick; De Jonghe, Peter; Depondt, Chantal; Dlugos, Dennis; Ferraro, Thomas N.; French, Jacqueline; Grenier-Boley, Benjamin; Hjalgrim, Helle; Jamnadas-Khoda, Jennifer; Kälviäinen, Reetta; Kunz, Wolfram S.; Lerche, Holger; Leu, Costin; Lindhout, Dick; Lo, Warren; Lowenstein, Daniel; McCormack, Mark; Chouraki, Vincent; Møller, Rikke S.; Molloy, Anne; Ng, Ping-Wing; Oliver, Karen; Privitera, Michael; Radtke, Rodney; Ruppert, Ann-Kathrin; Sander, Thomas; Schachter, Steven; Schankin, Christoph; Kamatani, Yoichiro; Scheffer, IngridDisorders 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.
- Characterization and expression analysis of a CNV at chromosome 10q22 encompassing 14 genes in an autistic patientPublication . C. Conceição, Inês; Correia, Catarina; Oliveira, Bárbara; Duque, Frederico; Mouga, Susana; Oliveira, Guiomar; M. Vicente, AstridAutism Spectrum Disorders (ASD) have a strong genetic component, with an estimated heritability of over 90%. Recent studies carried out by the Autism Genome Project (AGP) consortium suggest that rare Copy Number Variants (CNV), characterized by submicroscopic chromosomal deletions and duplications, are more frequent in ASD compared to controls, and may play an important role in susceptibility to this disorder. However, to adequately assess pathogenicity, a detailed characterization of patients CNVs is required. We have been characterizing potentially pathogenic rare CNVs identified by the AGP whole genome CNV analysis of 1,275 ASD individuals. CNV validation in patients and parents and characterization were performed by qPCR and Long-range PCR. One autistic patient showed a rare deletion absent in 4964 controls of European ancestry with no psychiatric disease history. This deletion was located at 10q22, and encompassed 14 genes, including ANXA7, ZMYND17, PPP3CB and CAMK2G. We validated this CNV as de novo, and accurate breakpoint determination showed that it is smaller than predicted by CNV identification algorithms, including only part of CAMK2G. We found that a 39 nucleotide addition occurred with the deletion, a mutational mechanism previously observed in other CNVs. Expression analysis of ANXA7, ZMYND17 and PPP3CB in this patient, in comparison with controls, is ongoing. Previous studies identified a genetic association of the ANXA7, PPP3CB and ZMYND17 region with schizophrenia, and significant expression alterations in schizophrenic patients. ANXA7 encodes Annexin7, involved in membrane fusion; interestingly, CNVs in other Annexin genes (ANXA1) have been found in ASD. PPP3CB plays an important role in synaptic plasticity, learning and memory. ZMYND17 has no known function. Our results suggest that alterations in these genes may be risk factors co-observed in autism and schizophrenia. Additional genetic and functional studies may lead to a better understanding of the common pathways between these neuropsychiatric disorders.
- CNV Characterization, Inheritance and Phenotypic Correlations in Families With AutismPublication . C. Conceição, Inês; Correia, Catarina; Oliveira, Bárbara; M. Rama, Maria; Café, Cátia; Almeida, Joana; Mouga, Susana; Duque, Frederico; Oliveira, Guiomar; M. Vicente, AstridAutism Spectrum Disorders (ASD) have a strong genetic component, with an estimated heritability of over 90%1. Recent studies carried out by the Autism Genome Project (AGP) consortium suggest that rare Copy Number Variants (CNVs), characterized by submicroscopic chromosomal deletions and duplications, are more frequent in ASD compared to controls, and may play an important role in susceptibility to this disorder2. However, to adequately assess pathogenicity, a detailed characterization of patients CNVs and phenotype is required. The goal of this study was to establish the clinical and etiological relevance for ASD of potentially pathogenic CNVs identified in a Portuguese population sample by whole genome CNV analysis, through the detailed characterization of CNVs and correlation with clinical phenotypes. Analysis of the AGP genome-wide CNV results using 1M SNP microarray2 identified a total of 14218 CNVs in 342 Portuguese probands. We selected 291 CNVs, present in 191 individuals (19 females and 172 males), using the following criteria: 1) CNVs that contained implicated/candidate genes for ASD; 2) CNVs in genomic regions known to be implicated/candidate for ASD; 3) CNVs in regions associated with syndromes with ASD symptoms; and 4) high confidence CNVs that did not overlap more than 20% with controls in available databases. We explored recurrence rates, genic content, regulatory elements, inheritance patterns and phenotypic correlations.
- Evidence for an association of prenatal exposure to particulate matter with clinical severity of Autism Spectrum DisorderPublication . Santos, João Xavier; Sampaio, Pedro; Rasga, Célia; Martiniano, Hugo; Faria, Clarissa; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Oliveira, Guiomar; Sousa, Lisete; Nunes, Ana; Moura Vicente, AstridEarly-life exposure to air pollutants, including ozone (O3), particulate matter (PM2.5 or PM10, depending on diameter of particles), nitrogen dioxide (NO2) and sulfur dioxide (SO2) has been suggested to contribute to the etiology of Autism Spectrum Disorder (ASD). In this study, we used air quality monitoring data to examine whether mothers of children with ASD were exposed to high levels of air pollutants during critical periods of pregnancy, and if higher exposure levels may lead to a higher clinical severity in their offspring. We used public data from the Portuguese Environment Agency to estimate exposure to these pollutants during the first, second and third trimesters of pregnancy, full pregnancy and first year of life of the child, for 217 subjects with ASD born between 2003 and 2016. These subjects were stratified in two subgroups according to clinical severity, as defined by the Autism Diagnostic Observational Schedule (ADOS). For all time periods, the average levels of PM2.5, PM10 and NO2 to which the subjects were exposed were within the admissible levels defined by the European Union. However, a fraction of these subjects showed exposure to levels of PM2.5 and PM10 above the admissible threshold. A higher clinical severity was associated with higher exposure to PM2.5 (p = 0.001), NO2 (p = 0.011) and PM10 (p = 0.041) during the first trimester of pregnancy, when compared with milder clinical severity. After logistic regression, associations with higher clinical severity were identified for PM2.5 exposure during the first trimester (p = 0.002; OR = 1.14, 95%CI: 1.05–1.23) and full pregnancy (p = 0.04; OR = 1.07, 95%CI: 1.00–1.15) and for PM10 (p = 0.02; OR = 1.07, 95%CI: 1.01–1.14) exposure during the third trimester. Exposure to PM is known to elicit neuropathological mechanisms associated with ASD, including neuroinflammation, mitochondrial disruptions, oxidative stress and epigenetic changes. These results offer new insights on the impact of earlylife exposure to PM in ASD clinical severity.
- Phenotypic categorization of putative pathogenic CNVs in a population of Autism Spectrum Disorder patientsPublication . Conceição, Inês C.; Correia, Catarina; Oliveira, Bárbara; Rama, Maria M.; Café, Cátia; Almeida, Joana; Mouga, Susana; Duque, Frederico; Oliveira, Guiomar; Vicente, A.M.
- Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disordersPublication . Weiner, Daniel J.; Wigdor, Emilie M.; Ripke, Stephan; Walters, Raymond K.; Kosmicki, Jack A.; Grove, Jakob; Samocha, Kaitlin E.; Goldstein, Jacqueline I.; Okbay, Aysu; Bybjerg-Grauholm, Jonas; Werge, Thomas; Minshew, Nancy; Merikangas, Alison; McMahon, William M.; McGrew, Susan G.; Ladd-Acosta, Christine; Mattheisen, Manuel; Hougaard, David M.; Jacob, Suma; Bishop, Somer; Iliadou, Bozenna; Arking, Dan E.; Hultman, Christina M.; Hertz-Picciotto, Irva; Hendren, Robert; Hansen, Christine S.; Haines, Jonathan L.; Guter, Stephen J.; Grice, Dorothy E.; Green, Jonathan M.; Taylor, Jacob; Mortensen, Preben Bo; Skuse, David; Green, Andrew; Goldberg, Arthur P.; Gillberg, Christopher; Gilbert, John; Gallagher, Louise; Freitag, Christine M.; Fombonne, Eric; Folstein, Susan E.; Fernandez, Bridget; Fallin, M Daniele; Devlin, Bernie; Børglum, Anders D.; Bækvad-Hansen, Marie; Ercan-Sencicek, A Gulhan; Ennis, Sean; Duque, Frederico; Duketis, Eftichia; Delorme, Richard; De Rubeis, Silvia; De Jonge, Maretha V.; Dawson, Geraldine; Anney, Richard; Cuccaro, Michael L.; Smith, George Davey; Correia, Catarina T.; Dumont, Ashley; Conroy, Judith; Conceição, Inês C.; Chiocchetti, Andreas G.; Celestino-Soper, Patrícia B.S.; Casey, Jillian; Cantor, Rita M.; Mattheisen, Manuel; Café, Cátia; Brennan, Sean; Daly, Mark J.; Bourgeron, Thomas; Bolton, Patrick F.; Hansen, Christine; Bölte, Sven; Bolshakova, Nadia; Betancur, Catalina; Bernier, Raphael; Sanders, Stephan J.; Beaudet, Arthur L.; Battaglia, Agatino; Bal, Vanessa H.; Robinson, Elise B.; Baird, Gillian; Bailey, Anthony J.; Bækvad-Hansen, Marie; Hansen, Thomas F.; Bader, Joel S.; Bacchelli, Elena; Nordentoft, Merete; Anagnostou, Evdokia; Amaral, David; Almeida, Joana; Buxbaum, Joseph D.; Moran, Jennifer; Chakravarti, Aravinda; Cook, Edwin H.; Coon, Hilary; Geschwind, Daniel H.; Howrigan, Daniel; Nørgaard-Pedersen, Bent; Gill, Michael; Hakonarson, Hakon; Hallmayer, Joachim; Palotie, Aarno; Santangelo, Susan; Mors, Ole; Sutcliffe, James S.; Lowe, Jennifer K.; Poterba, Timothy; Martsenkovsky, Igor; Poulsen, Jesper; Stevens, Christine; Anttila, Verneri; Holmans, Peter; Huang, Hailiang; Klei, Lambertus; Lee, Phil H; Medland, Sarah E.; Neale, Benjamin; Lord, Catherine; Martin, Donna M.; Weiss, Lauren A.; Zwaigenbaum, Lonnie; Yu, Timothy W.; Wittemeyer, Kerstin; Willsey, A Jeremy; Wijsman, Ellen M; Wassink, Thomas H.; Waltes, Regina; Walsh, Christopher A.; Wallace, Simon; Mane, Shrikant M.; Levitt, Pat; Vorstman, Jacob A.S.; Vieland, Veronica J.; Vicente, Astrid M.; van Engeland, Herman; Tsang, Kathryn; Thompson, Ann P.; Szatmari, Peter; Svantesson, Oscar; Steinberg, Stacy; Magnusson, Pall; Stefansson, Kari; Martin, Christa Lese; Stefansson, Hreinn; State, Matthew W.; Soorya, Latha; Silagadze, Teimuraz; Scherer, Stephen W.; Schellenberg, Gerard D.; Sandin, Sven; Saemundsen, Evald; Magalhaes, Tiago; Rouleau, Guy A.; Rogé, Bernadette; Ledbetter, David H.; Roeder, Kathryn; Roberts, Wendy; Reichert, Jennifer; Reichenberg, Abraham; Rehnström, Karola; Regan, Regina; Poustka, Fritz; Maestrini, Elena; Poultney, Christopher S.; Piven, Joseph; Pinto, Dalila; Leboyer, Marion; Pericak-Vance, Margaret A.; Pejovic-Milovancevic, Milica; Pedersen, Marianne G.; Pedersen, Carsten B.; Paterson, Andrew D.; Parr, Jeremy R.; Kolevzon, Alexander; Pagnamenta, Alistair T.; Oliveira, Guiomar; Nurnberger, John I.; Nordentoft, Merete; Le Couteur, Ann S.; Murtha, Michael T.; Mouga, Susana; Mors, Ole; Morrow, Eric M.; De Luca, Daniel Moreno; Klauck, Sabine M.; Monaco, Anthony P.Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
- Prevalence of Autism Spectrum Disorder in the Centro region of Portugal: a population based study of school age children within the ASDEU projectPublication . Rasga, Célia; Santos, João Xavier; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Posada, Manuel; Nunes, Ana; Oliveira, Guiomar; Vicente, Astrid MouraIntroduction: Accurate prevalence estimates for Autism Spectrum Disorder (ASD) are fundamental to adequately program medical and educational resources for children. However, estimates vary globally and across Europe, and it is therefore wise to conduct epidemiological studies in defined geo-cultural contexts. Methods: We used a population screening approach to estimate the prevalence of ASD in the Centro region of Portugal, using a harmonized protocol as part of the Autism Spectrum Disorders in the European Union (ASDEU) project. Results: The overall prevalence was estimated at 0.5% (95% CI 0.3-0.7), higher in schools with Autism Units (3.3%, 95%CI 2.7-3.9) than in regular schools (0.3%, 95% CI 0.1-0.5) or schools with Multiple Disability Units (0.3%, 95% CI 0.04-0.6). Discussion: The results indicate that the diagnosis of ASD is followed by the most effective educational policies in Centro Region. The variability in prevalence estimates across the different regions from the ASDEU project, and globally, is discussed.
- Prevalência da perturbação do espectro do autismo na região Centro de Portugal: um estudo no âmbito do projeto ASDEUPublication . Rasga, Célia; Santos, João Xavier; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Nunes, Ana; Oliveira, Guiomar; Vicente, Astrid MouraA prevalência da perturbação do espectro do autismo (PEA) em crianças foi estimada na região Centro de Portugal, no âmbito do projeto Autism Spectrum Disorders in the European Union (ASDEU). A metodologia de estudo baseou-se no rastreio de crianças entre os 7 e 9 anos matriculadas, no ano letivo de 2016/2017, em escolas primárias desta região. O rastreio incluiu todas as escolas com unidades de apoio especializado para crianças com problemas de neurodesenvolvimento e cerca de 10% das escolas regulares, selecionadas aleatoriamente. A sinalização das crianças foi feita pelos professores com recurso a um questionário estruturado, previamente validado, após consentimento parental. O diagnóstico foi feito através de avaliação clínica e funcional direta por equipa clínica especializada. Foram rastreadas 13 690 crianças de 173 escolas. A prevalência estimada para a PEA na região Centro foi de 0,5% (IC95% 0,3-0,7). Nas escolas com unidades de apoio especializado para autismo, observou-se uma prevalência substancialmente mais elevada de 3,3% (IC95% 2,7-3,9), indicando que a maioria das crianças está a receber o apoio educativo mais indicado. A prevalência de PEA na região Centro foi comparável a outros países envolvidos no projeto ASDEU, tendo-se, no entanto, observado assimetrias regionais na Europa.
- Prevalência da perturbação do espectro do autismo na região Centro de Portugal: Um estudo no âmbito do projeto ASDEUPublication . Rasga, Célia; Santos, João; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Nunes, Ana; Oliveira, Guiomar; Vicente, AstridA prevalência da perturbação do espectro do autismo (PEA) em crianças foi estimada na região Centro de Portugal, no âmbito do projeto Autism Spectrum Disorders in the European Union (ASDEU). A metodologia de estudo baseou-se no rastreio de crianças entre os 7 e 9 anos matricula- das, no ano letivo de 2016/2017, em escolas primárias desta região. O rastreio incluiu todas as escolas com unidades de apoio especializado para crianças com problemas de neurodesenvolvimento e cerca de 10% das escolas regulares, selecionadas aleatoriamente. A sinalização das crianças foi feita pelos professores com recurso a um questionário estruturado, previamente validado, após consentimento parental. O diagnóstico foi feito através de avaliação clínica e funcional direta por equipa clínica especializada. Foram rastreadas 13 690 crianças de 173 escolas. A prevalência estimada para a PEA na região Centro foi de 0,5% (IC95% 0,3-0,7). Nas escolas com unidades de apoio especializado para autismo, observou-se uma prevalência substancialmente mais elevada de 3,3% (IC95% 2,7-3,9), indicando que a maioria das crianças está a receber o apoio educativo mais indicado. A prevalência de PEA na região Centro foi comparável a outros países envolvidos no projeto ASDEU, tendo-se, no entanto, observado assimetrias regionais na Europa.
- Relevance of Common and Rare CNVs for Autism EtiologyPublication . C. Conceição, Inês; Correia, Catarina; Oliveira, Bárbara; Rama, Maria Margarida; Café, Cátia; Almeida, Joana; Mouga, Susana; Duque, Frederico; Oliveira, Guiomar; M. Vicente, AstridRecent reports by the Autism Genome Project (AGP) consortium and other groups show that Copy Number Variants (CNVs), while individually rare, collectively may explain a large fraction of the etiology of Autism Spectrum Disorders (ASD). The goal of this study was to establish the clinical and etiological relevance for ASD of potentially pathogenic CNVs identified in a Portuguese population sample by whole genome CNV analysis, through the detailed characterization of CNVs and correlation with clinical phenotypes. Analysis of the Autism Genome Project genome-wide CNV results using 1M SNP microarray1 identified a total of 14218 CNVs in 342 Portuguese probands. We selected 292 CNVs, present in 191 individuals (19 females and 172 males), using the following criteria: 1) CNVs that contained implicated/candidate genes for ASD; 2) CNVs in genomic regions known to be implicated/candidate for ASD; 3) CNVs containing genes associated with syndromes with ASD symptoms; and 4) high confidence CNVs that did not overlap more than 20% with controls in available databases. We explored recurrence rates, genic content, regulatory elements, inheritance patterns and clinical correlations