The genetics care pathway experienced by families affected by autism spectrum disorder (ASD) around the time of diagnosis is currently uncharacterized and potentially variable across contexts. The lack of consensus on outcome measures to capture the impact of genetic services for these families shows a gap in understanding and optimizing this genetics care pathway. The Genetic Counseling Outcome Scale (GCOS-24) is a validated outcome measure of clinical genetics services. The current study aims to adapt and validate the GCOS-24 as an outcome measure in the context routine genetic testing in ASD and related conditions. Families seen for their child's developmental evaluation for ASD and related conditions were invited to participate in a genomics cohort between 2016 and 2018. Families (n = 111) completed the mGCOS-24 (modified GCOS-24), adapted from the original GCOS-24 by clinicians working in the target population's routine care pathway. The mGCOS-24 has acceptable internal consistency (Cronbach's α = 0.84) and high test-retest reliability (ICC = 0.88). It also inversely correlates with stress as measured by Perceived Stress Scale (PSS-10) and distress, as measured by the Distress Thermometer, rs ≥ 0.39, ps < 0.001. The mGCOS-24 had adequate readability, as supported by cognitive interviews completed by a sub-sample of five mothers of a child with ASD. Together, our findings show that the mGCOS-24 has good validity for the target population. Preliminary characterization of the genetics care pathway in this population revealed remarkable variability in pre-test counseling and limited post-test counseling. The use of the mGCOS-24 as an outcome measure is useful in filling some of these gaps by offering a way to assess, and in the future, optimize the genetics care pathway for families affected by autism and related neurodevelopmental conditions.

U1 - https://www.ncbi.nlm.nih.gov/pubmed/32893416?dopt=Abstract ER - TY - JOUR T1 - Perceived utility of biological testing for autism spectrum disorder is associated with child and family functioning. JF - Res Dev Disabil Y1 - 2020 A1 - Yusuf, Afiqah A1 - Peltekova, Iskra A1 - Savion-Lemieux, Tal A1 - Frei, Jennifer A1 - Bruno, Ruth A1 - Joober, Ridha A1 - Howe, Jennifer A1 - Scherer, Stephen W A1 - Elsabbagh, Mayada AB -**BACKGROUND: **The clinical integration of chromosomal microarray testing promises improvements in diagnostic yields in Autism Spectrum Disorder (ASD). While the impact on clinical management is promising for some families, the utility perceived by families, including the majority for whom results are negative, is unclear. With next generation genomic sequencing technologies poised for integration, along with promising ASD biomarkers being developed, there is a need to understand the extent to which genomic and other biological testing would have utility for the target recipients of these tests and their families. The purpose of the present cross-sectional study was to examine the predictors of perceived utility of biological testing among parents of a child with ASD.

**METHODS: **The Perceived Utility of Biotesting (PUB) Questionnaire was developed based on literature review and integrating family review. Following their child's diagnosis, families participating in an ongoing prospective study completed the PUB questionnaire along with self-reported measures of parent stress, child and family functioning, and family-centered care prior to undergoing genetic testing for both clinical and research purposes.

**RESULTS: **Based on n = 85 families, psychometric properties of the Perceived Utility of Biotesting questionnaire suggest a reliable and valid instrument. A stepwise regression analysis reveals that lower levels of child emotional and behavioural functioning and higher levels of family functioning correlated with higher perceived utility for biological testing.

**LIMITATIONS: **A main limitation in the study is the participation rate of 50 %, thus the possibility of self-selection bias cannot be ruled out. We also chose to assess perceived utility among parents rather than the individuals with ASD themselves: modifying the questionnaire to capture perceived utility from autistic individuals across the lifespan would prove essential in future studies. Finally, ongoing validation of the PUB by assessing the PUB's discriminant and convergent validity is still needed.

**CONCLUSIONS: **We conclude that the utility of biological testing perceived by families whose child is undergoing genetic testing around ASD diagnosis depends on their unique child and family characteristics. This signifies that engaging families in biomarker discovery for improving the impact of research and care requires systematic input from a representative sample of families.

Understanding the overall utility of biological testing for autism spectrum disorder (ASD) is essential for the development and integration of biomarkers into routine care. One measure related to the overall utility of biological testing is the knowledge that a person has about the condition he/she suffers from. However, a major gap towards understanding the role of knowledge in overall utility is the absence of studies that have assessed knowledge of autism along with its predictors within a representative sample of families within the context of routine care. The objective of this study was to measure knowledge of ASD among families within the routine care pathway for biological testing in ASD by examining the association between knowledge with potential correlates of knowledge namely sociodemographic factors, parental stress and distress, and time since diagnosis among parents whose child with ASD is undergoing clinical genetic testing. Parents of a child diagnosed with ASD (n = 85, Mage = 39.0, SD = 7.7) participating in an ongoing prospective genomics study completed the ASD Quiz prior to undergoing genetic testing for clinical and research purposes. Parents also completed self-reported measures of stress and distress. Parent stress and distress was each independently correlated with knowledge of ASD, rs ≥ 0.26, ps < 0.05. Stepwise regression analysis revealed a significant model accounting for 7.8% of the variance in knowledge, F (1, 82) = 8.02, p = 0.006. The only factor significantly associated with knowledge was parental distress, β = 0.30, p = 0.006. Parental stress, time since diagnosis, and sociodemographic factors were not significant predictors in this model. We concluded that families require tailored support prior to undergoing genetic testing to address either knowledge gaps or high distress. Ongoing appraisal of the testing process among families of diverse backgrounds is essential in offering optimal care for families undergoing genetic testing.

VL - 14 IS - 9 U1 - https://www.ncbi.nlm.nih.gov/pubmed/31557237?dopt=Abstract ER - TY - JOUR T1 - Analysis of shared heritability in common disorders of the brain. JF - Science Y1 - 2018 A1 - Anttila, Verneri A1 - Bulik-Sullivan, Brendan A1 - Finucane, Hilary K A1 - Walters, Raymond K A1 - Bras, Jose A1 - Duncan, Laramie A1 - Escott-Price, Valentina A1 - Falcone, Guido J A1 - Gormley, Padhraig A1 - Malik, Rainer A1 - Patsopoulos, Nikolaos A A1 - Ripke, Stephan A1 - Wei, Zhi A1 - Yu, Dongmei A1 - Lee, Phil H A1 - Turley, Patrick A1 - Grenier-Boley, Benjamin A1 - Chouraki, Vincent A1 - Kamatani, Yoichiro A1 - Berr, Claudine A1 - Letenneur, Luc A1 - Hannequin, Didier A1 - Amouyel, Philippe A1 - Boland, Anne A1 - Deleuze, Jean-François A1 - Duron, Emmanuelle A1 - Vardarajan, Badri N A1 - Reitz, Christiane A1 - Goate, Alison M A1 - Huentelman, Matthew J A1 - Kamboh, M Ilyas A1 - Larson, Eric B A1 - Rogaeva, Ekaterina A1 - St George-Hyslop, Peter A1 - Hakonarson, Hakon A1 - Kukull, Walter A A1 - Farrer, Lindsay A A1 - Barnes, Lisa L A1 - Beach, Thomas G A1 - Demirci, F Yesim A1 - Head, Elizabeth A1 - Hulette, Christine M A1 - Jicha, Gregory A A1 - Kauwe, John S K A1 - Kaye, Jeffrey A A1 - Leverenz, James B A1 - Levey, Allan I A1 - Lieberman, Andrew P A1 - Pankratz, Vernon S A1 - Poon, Wayne W A1 - Quinn, Joseph F A1 - Saykin, Andrew J A1 - Schneider, Lon S A1 - Smith, Amanda G A1 - Sonnen, Joshua A A1 - Stern, Robert A A1 - Van Deerlin, Vivianna M A1 - Van Eldik, Linda J A1 - Harold, Denise A1 - Russo, Giancarlo A1 - Rubinsztein, David C A1 - Bayer, Anthony A1 - Tsolaki, Magda A1 - Proitsi, Petra A1 - Fox, Nick C A1 - Hampel, Harald A1 - Owen, Michael J A1 - Mead, Simon A1 - Passmore, Peter A1 - Morgan, Kevin A1 - Nöthen, Markus M A1 - Rossor, Martin A1 - Lupton, Michelle K A1 - Hoffmann, Per A1 - Kornhuber, Johannes A1 - Lawlor, Brian A1 - McQuillin, Andrew A1 - Al-Chalabi, Ammar A1 - Bis, Joshua C A1 - Ruiz, Agustin A1 - Boada, Mercè A1 - Seshadri, Sudha A1 - Beiser, Alexa A1 - Rice, Kenneth A1 - van der Lee, Sven J A1 - De Jager, Philip L A1 - Geschwind, Daniel H A1 - Riemenschneider, Matthias A1 - Riedel-Heller, Steffi A1 - Rotter, Jerome I A1 - Ransmayr, Gerhard A1 - Hyman, Bradley T A1 - Cruchaga, Carlos A1 - Alegret, Montserrat A1 - Winsvold, Bendik A1 - Palta, Priit A1 - Farh, Kai-How A1 - Cuenca-Leon, Ester A1 - Furlotte, Nicholas A1 - Kurth, Tobias A1 - Ligthart, Lannie A1 - Terwindt, Gisela M A1 - Freilinger, Tobias A1 - Ran, Caroline A1 - Gordon, Scott D A1 - Borck, Guntram A1 - Adams, Hieab H H A1 - Lehtimäki, Terho A1 - Wedenoja, Juho A1 - Buring, Julie E A1 - Schürks, Markus A1 - Hrafnsdottir, Maria A1 - Hottenga, Jouke-Jan A1 - Penninx, Brenda A1 - Artto, Ville A1 - Kaunisto, Mari A1 - Vepsäläinen, Salli A1 - Martin, Nicholas G A1 - Montgomery, Grant W A1 - Kurki, Mitja I A1 - Hämäläinen, Eija A1 - Huang, Hailiang A1 - Huang, Jie A1 - Sandor, Cynthia A1 - Webber, Caleb A1 - Müller-Myhsok, Bertram A1 - Schreiber, Stefan A1 - Salomaa, Veikko A1 - Loehrer, Elizabeth A1 - Göbel, Hartmut A1 - Macaya, Alfons A1 - Pozo-Rosich, Patricia A1 - Hansen, Thomas A1 - Werge, Thomas A1 - Kaprio, Jaakko A1 - Metspalu, Andres A1 - Kubisch, Christian A1 - Ferrari, Michel D A1 - Belin, Andrea C A1 - van den Maagdenberg, Arn M J M A1 - Zwart, John-Anker A1 - Boomsma, Dorret A1 - Eriksson, Nicholas A1 - Olesen, Jes A1 - Chasman, Daniel I A1 - Nyholt, Dale R A1 - Avbersek, Andreja A1 - Baum, Larry A1 - Berkovic, Samuel A1 - Bradfield, Jonathan A1 - Buono, Russell A1 - Catarino, Claudia B A1 - Cossette, Patrick A1 - De Jonghe, Peter A1 - Depondt, Chantal A1 - Dlugos, Dennis A1 - Ferraro, Thomas N A1 - French, Jacqueline A1 - Hjalgrim, Helle A1 - Jamnadas-Khoda, Jennifer A1 - Kälviäinen, Reetta A1 - Kunz, Wolfram S A1 - Lerche, Holger A1 - Leu, Costin A1 - Lindhout, Dick A1 - Lo, Warren A1 - Lowenstein, Daniel A1 - McCormack, Mark A1 - Møller, Rikke S A1 - Molloy, Anne A1 - Ng, Ping-Wing A1 - Oliver, Karen A1 - Privitera, Michael A1 - Radtke, Rodney A1 - Ruppert, Ann-Kathrin A1 - Sander, Thomas A1 - Schachter, Steven A1 - Schankin, Christoph A1 - Scheffer, Ingrid A1 - Schoch, Susanne A1 - Sisodiya, Sanjay M A1 - Smith, Philip A1 - Sperling, Michael A1 - Striano, Pasquale A1 - Surges, Rainer A1 - Thomas, G Neil A1 - Visscher, Frank A1 - Whelan, Christopher D A1 - Zara, Federico A1 - Heinzen, Erin L A1 - Marson, Anthony A1 - Becker, Felicitas A1 - Stroink, Hans A1 - Zimprich, Fritz A1 - Gasser, Thomas A1 - Gibbs, Raphael A1 - Heutink, Peter A1 - Martinez, Maria A1 - Morris, Huw R A1 - Sharma, Manu A1 - Ryten, Mina A1 - Mok, Kin Y A1 - Pulit, Sara A1 - Bevan, Steve A1 - Holliday, Elizabeth A1 - Attia, John A1 - Battey, Thomas A1 - Boncoraglio, Giorgio A1 - Thijs, Vincent A1 - Chen, Wei-Min A1 - Mitchell, Braxton A1 - Rothwell, Peter A1 - Sharma, Pankaj A1 - Sudlow, Cathie A1 - Vicente, Astrid A1 - Markus, Hugh A1 - Kourkoulis, Christina A1 - Pera, Joana A1 - Raffeld, Miriam A1 - Silliman, Scott A1 - Boraska Perica, Vesna A1 - Thornton, Laura M A1 - Huckins, Laura M A1 - William Rayner, N A1 - Lewis, Cathryn M A1 - Gratacos, Monica A1 - Rybakowski, Filip A1 - Keski-Rahkonen, Anna A1 - Raevuori, Anu A1 - Hudson, James I A1 - Reichborn-Kjennerud, Ted A1 - Monteleone, Palmiero A1 - Karwautz, Andreas A1 - Mannik, Katrin A1 - Baker, Jessica H A1 - O'Toole, Julie K A1 - Trace, Sara E A1 - Davis, Oliver S P A1 - Helder, Sietske G A1 - Ehrlich, Stefan A1 - Herpertz-Dahlmann, Beate A1 - Danner, Unna N A1 - van Elburg, Annemarie A A1 - Clementi, Maurizio A1 - Forzan, Monica A1 - Docampo, Elisa A1 - Lissowska, Jolanta A1 - Hauser, Joanna A1 - Tortorella, Alfonso A1 - Maj, Mario A1 - Gonidakis, Fragiskos A1 - Tziouvas, Konstantinos A1 - Papezova, Hana A1 - Yilmaz, Zeynep A1 - Wagner, Gudrun A1 - Cohen-Woods, Sarah A1 - Herms, Stefan A1 - Julià, Antonio A1 - Rabionet, Raquel A1 - Dick, Danielle M A1 - Ripatti, Samuli A1 - Andreassen, Ole A A1 - Espeseth, Thomas A1 - Lundervold, Astri J A1 - Steen, Vidar M A1 - Pinto, Dalila A1 - Scherer, Stephen W A1 - Aschauer, Harald A1 - Schosser, Alexandra A1 - Alfredsson, Lars A1 - Padyukov, Leonid A1 - Halmi, Katherine A A1 - Mitchell, James A1 - Strober, Michael A1 - Bergen, Andrew W A1 - Kaye, Walter A1 - Szatkiewicz, Jin Peng A1 - Cormand, Bru A1 - Ramos-Quiroga, Josep Antoni A1 - Sánchez-Mora, Cristina A1 - Ribasés, Marta A1 - Casas, Miguel A1 - Hervas, Amaia A1 - Arranz, Maria Jesús A1 - Haavik, Jan A1 - Zayats, Tetyana A1 - Johansson, Stefan A1 - Williams, Nigel A1 - Dempfle, Astrid A1 - Rothenberger, Aribert A1 - Kuntsi, Jonna A1 - Oades, Robert D A1 - Banaschewski, Tobias A1 - Franke, Barbara A1 - Buitelaar, Jan K A1 - Arias Vasquez, Alejandro A1 - Doyle, Alysa E A1 - Reif, Andreas A1 - Lesch, Klaus-Peter A1 - Freitag, Christine A1 - Rivero, Olga A1 - Palmason, Haukur A1 - Romanos, Marcel A1 - Langley, Kate A1 - Rietschel, Marcella A1 - Witt, Stephanie H A1 - Dalsgaard, Soeren A1 - Børglum, Anders D A1 - Waldman, Irwin A1 - Wilmot, Beth A1 - Molly, Nikolas A1 - Bau, Claiton H D A1 - Crosbie, Jennifer A1 - Schachar, Russell A1 - Loo, Sandra K A1 - McGough, James J A1 - Grevet, Eugenio H A1 - Medland, Sarah E A1 - Robinson, Elise A1 - Weiss, Lauren A A1 - Bacchelli, Elena A1 - Bailey, Anthony A1 - Bal, Vanessa A1 - Battaglia, Agatino A1 - Betancur, Catalina A1 - Bolton, Patrick A1 - Cantor, Rita A1 - Celestino-Soper, Patrícia A1 - Dawson, Geraldine A1 - De Rubeis, Silvia A1 - Duque, Frederico A1 - Green, Andrew A1 - Klauck, Sabine M A1 - Leboyer, Marion A1 - Levitt, Pat A1 - Maestrini, Elena A1 - Mane, Shrikant A1 - De-Luca, Daniel Moreno- A1 - Parr, Jeremy A1 - Regan, Regina A1 - Reichenberg, Abraham A1 - Sandin, Sven A1 - Vorstman, Jacob A1 - Wassink, Thomas A1 - Wijsman, Ellen A1 - Cook, Edwin A1 - Santangelo, Susan A1 - Delorme, Richard A1 - Rogé, Bernadette A1 - Magalhaes, Tiago A1 - Arking, Dan A1 - Schulze, Thomas G A1 - Thompson, Robert C A1 - Strohmaier, Jana A1 - Matthews, Keith A1 - Melle, Ingrid A1 - Morris, Derek A1 - Blackwood, Douglas A1 - McIntosh, Andrew A1 - Bergen, Sarah E A1 - Schalling, Martin A1 - Jamain, Stephane A1 - Maaser, Anna A1 - Fischer, Sascha B A1 - Reinbold, Céline S A1 - Fullerton, Janice M A1 - Guzman-Parra, José A1 - Mayoral, Fermin A1 - Schofield, Peter R A1 - Cichon, Sven A1 - Mühleisen, Thomas W A1 - Degenhardt, Franziska A1 - Schumacher, Johannes A1 - Bauer, Michael A1 - Mitchell, Philip B A1 - Gershon, Elliot S A1 - Rice, John A1 - Potash, James B A1 - Zandi, Peter P A1 - Craddock, Nick A1 - Ferrier, I Nicol A1 - Alda, Martin A1 - Rouleau, Guy A A1 - Gustavo Turecki A1 - Ophoff, Roel A1 - Pato, Carlos A1 - Anjorin, Adebayo A1 - Stahl, Eli A1 - Leber, Markus A1 - Czerski, Piotr M A1 - Cruceanu, Cristiana A1 - Jones, Ian R A1 - Posthuma, Danielle A1 - Andlauer, Till F M A1 - Forstner, Andreas J A1 - Streit, Fabian A1 - Baune, Bernhard T A1 - Air, Tracy A1 - Sinnamon, Grant A1 - Wray, Naomi R A1 - MacIntyre, Donald J A1 - Porteous, David A1 - Homuth, Georg A1 - Rivera, Margarita A1 - Grove, Jakob A1 - Middeldorp, Christel M A1 - Hickie, Ian A1 - Pergadia, Michele A1 - Mehta, Divya A1 - Smit, Johannes H A1 - Jansen, Rick A1 - de Geus, Eco A1 - Dunn, Erin A1 - Li, Qingqin S A1 - Nauck, Matthias A1 - Schoevers, Robert A A1 - Beekman, Aartjan Tf A1 - Knowles, James A A1 - Viktorin, Alexander A1 - Arnold, Paul A1 - Barr, Cathy L A1 - Bedoya-Berrio, Gabriel A1 - Bienvenu, O Joseph A1 - Brentani, Helena A1 - Burton, Christie A1 - Camarena, Beatriz A1 - Cappi, Carolina A1 - Cath, Danielle A1 - Cavallini, Maria A1 - Cusi, Daniele A1 - Darrow, Sabrina A1 - Denys, Damiaan A1 - Derks, Eske M A1 - Dietrich, Andrea A1 - Fernandez, Thomas A1 - Figee, Martijn A1 - Freimer, Nelson A1 - Gerber, Gloria A1 - Grados, Marco A1 - Greenberg, Erica A1 - Hanna, Gregory L A1 - Hartmann, Andreas A1 - Hirschtritt, Matthew E A1 - Hoekstra, Pieter J A1 - Huang, Alden A1 - Huyser, Chaim A1 - Illmann, Cornelia A1 - Jenike, Michael A1 - Kuperman, Samuel A1 - Leventhal, Bennett A1 - Lochner, Christine A1 - Lyon, Gholson J A1 - Macciardi, Fabio A1 - Madruga-Garrido, Marcos A1 - Malaty, Irene A A1 - Maras, Athanasios A1 - McGrath, Lauren A1 - Miguel, Eurípedes C A1 - Mir, Pablo A1 - Nestadt, Gerald A1 - Nicolini, Humberto A1 - Okun, Michael S A1 - Pakstis, Andrew A1 - Paschou, Peristera A1 - Piacentini, John A1 - Pittenger, Christopher A1 - Plessen, Kerstin A1 - Ramensky, Vasily A1 - Ramos, Eliana M A1 - Reus, Victor A1 - Richter, Margaret A A1 - Riddle, Mark A A1 - Robertson, Mary M A1 - Roessner, Veit A1 - Rosário, Maria A1 - Samuels, Jack F A1 - Sandor, Paul A1 - Stein, Dan J A1 - Tsetsos, Fotis A1 - Van Nieuwerburgh, Filip A1 - Weatherall, Sarah A1 - Wendland, Jens R A1 - Wolanczyk, Tomasz A1 - Worbe, Yulia A1 - Zai, Gwyneth A1 - Goes, Fernando S A1 - McLaughlin, Nicole A1 - Nestadt, Paul S A1 - Grabe, Hans-Jorgen A1 - Depienne, Christel A1 - Konkashbaev, Anuar A1 - Lanzagorta, Nuria A1 - Valencia-Duarte, Ana A1 - Bramon, Elvira A1 - Buccola, Nancy A1 - Cahn, Wiepke A1 - Cairns, Murray A1 - Chong, Siow A A1 - Cohen, David A1 - Crespo-Facorro, Benedicto A1 - Crowley, James A1 - Davidson, Michael A1 - DeLisi, Lynn A1 - Dinan, Timothy A1 - Donohoe, Gary A1 - Drapeau, Elodie A1 - Duan, Jubao A1 - Haan, Lieuwe A1 - Hougaard, David A1 - Karachanak-Yankova, Sena A1 - Khrunin, Andrey A1 - Klovins, Janis A1 - Kučinskas, Vaidutis A1 - Lee Chee Keong, Jimmy A1 - Limborska, Svetlana A1 - Loughland, Carmel A1 - Lönnqvist, Jouko A1 - Maher, Brion A1 - Mattheisen, Manuel A1 - McDonald, Colm A1 - Murphy, Kieran C A1 - Nenadic, Igor A1 - van Os, Jim A1 - Pantelis, Christos A1 - Pato, Michele A1 - Petryshen, Tracey A1 - Quested, Digby A1 - Roussos, Panos A1 - Sanders, Alan R A1 - Schall, Ulrich A1 - Schwab, Sibylle G A1 - Sim, Kang A1 - So, Hon-Cheong A1 - Stögmann, Elisabeth A1 - Subramaniam, Mythily A1 - Toncheva, Draga A1 - Waddington, John A1 - Walters, James A1 - Weiser, Mark A1 - Cheng, Wei A1 - Cloninger, Robert A1 - Curtis, David A1 - Gejman, Pablo V A1 - Henskens, Frans A1 - Mattingsdal, Morten A1 - Oh, Sang-Yun A1 - Scott, Rodney A1 - Webb, Bradley A1 - Breen, Gerome A1 - Churchhouse, Claire A1 - Bulik, Cynthia M A1 - Daly, Mark A1 - Dichgans, Martin A1 - Faraone, Stephen V A1 - Guerreiro, Rita A1 - Holmans, Peter A1 - Kendler, Kenneth S A1 - Koeleman, Bobby A1 - Mathews, Carol A A1 - Price, Alkes A1 - Scharf, Jeremiah A1 - Sklar, Pamela A1 - Williams, Julie A1 - Wood, Nicholas W A1 - Cotsapas, Chris A1 - Palotie, Aarno A1 - Smoller, Jordan W A1 - Sullivan, Patrick A1 - Rosand, Jonathan A1 - Corvin, Aiden A1 - Neale, Benjamin M AB -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.

VL - 360 IS - 6395 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29930110?dopt=Abstract ER - TY - JOUR T1 - Cover Image, Volume 173A, Number 2, February 2017. JF - Am J Med Genet A Y1 - 2017 A1 - Maussion, Gilles A1 - Cruceanu, Cristiana A1 - Rosenfeld, Jill A A1 - Bell, Scott C A1 - Fabrice Jollant A1 - Szatkiewicz, Jin A1 - Collins, Ryan L A1 - Hanscom, Carrie A1 - Kolobova, Ilaria A1 - de Champfleur, Nicolas Menjot A1 - Blumenthal, Ian A1 - Chiang, Colby A1 - Ota, Vanessa A1 - Hultman, Christina A1 - O'Dushlaine, Colm A1 - McCarroll, Steve A1 - Alda, Martin A1 - Jacquemont, Sebastien A1 - Ordulu, Zehra A1 - Marshall, Christian R A1 - Carter, Melissa T A1 - Shaffer, Lisa G A1 - Sklar, Pamela A1 - Girirajan, Santhosh A1 - Morton, Cynthia C A1 - Gusella, James F A1 - Gustavo Turecki A1 - Stavropoulos, Dimitri J A1 - Sullivan, Patrick F A1 - Scherer, Stephen W A1 - Talkowski, Michael E A1 - Carl Ernst AB -The cover image, by Carl Ernst et al., is based on the Original Article Implication of LRRC4C and DPP6 in neurodevelopmental disorders, DOI: 10.1002/ajmg.a.38021.

VL - 173 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28102589?dopt=Abstract ER - TY - JOUR T1 - Implication of LRRC4C and DPP6 in neurodevelopmental disorders. JF - Am J Med Genet A Y1 - 2017 A1 - Maussion, Gilles A1 - Cruceanu, Cristiana A1 - Rosenfeld, Jill A A1 - Bell, Scott C A1 - Fabrice Jollant A1 - Szatkiewicz, Jin A1 - Collins, Ryan L A1 - Hanscom, Carrie A1 - Kolobova, Ilaria A1 - de Champfleur, Nicolas Menjot A1 - Blumenthal, Ian A1 - Chiang, Colby A1 - Ota, Vanessa A1 - Hultman, Christina A1 - O'Dushlaine, Colm A1 - McCarroll, Steve A1 - Alda, Martin A1 - Jacquemont, Sebastien A1 - Ordulu, Zehra A1 - Marshall, Christian R A1 - Carter, Melissa T A1 - Shaffer, Lisa G A1 - Sklar, Pamela A1 - Girirajan, Santhosh A1 - Morton, Cynthia C A1 - Gusella, James F A1 - Gustavo Turecki A1 - Stavropoulos, Dimitri J A1 - Sullivan, Patrick F A1 - Scherer, Stephen W A1 - Talkowski, Michael E A1 - Carl Ernst AB -We performed whole-genome sequencing on an individual from a family with variable psychiatric phenotypes that had a sensory processing disorder, apraxia, and autism. The proband harbored a maternally inherited balanced translocation (46,XY,t(11;14)(p12;p12)mat) that disrupted LRRC4C, a member of the highly specialized netrin G family of axon guidance molecules. The proband also inherited a paternally derived chromosomal inversion that disrupted DPP6, a potassium channel interacting protein. Copy Number (CN) analysis in 14,077 cases with neurodevelopmental disorders and 8,960 control subjects revealed that 60% of cases with exonic deletions in LRRC4C had a second clinically recognizable syndrome associated with variable clinical phenotypes, including 16p11.2, 1q44, and 2q33.1 CN syndromes, suggesting LRRC4C deletion variants may be modifiers of neurodevelopmental disorders. In vitro, functional assessments modeling patient deletions in LRRC4C suggest a negative regulatory role of these exons found in the untranslated region of LRRC4C, which has a single, terminal coding exon. These data suggest that the proband's autism may be due to the inheritance of disruptions in both DPP6 and LRRC4C, and may highlight the importance of the netrin G family and potassium channel interacting molecules in neurodevelopmental disorders. © 2016 Wiley Periodicals, Inc.

VL - 173 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27759917?dopt=Abstract ER -