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3. Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

Author

Barr, Cathy L., Batterson, James R., Berlin, Cheston, Budman, Cathy L., Coppola, Giovanni, Cox, Nancy J., Darrow, Sabrina, Dion, Yves, Freimer, Nelson B., Grados, Marco A., Greenberg, Erica, Hirschtritt, Matthew E., Huang, Alden Y., Illmann, Cornelia, King, Robert A., Kurlan, Roger, Leckman, James F., Lyon, Gholson J., Malaty, Irene A., McMahon, William M., Neale, Benjamin M., Okun, Michael S., Osiecki, Lisa, Robertson, Mary M., Rouleau, Guy A., Sandor, Paul, Singer, Harvey S., Smit, Jan H., Sul, Jae Hoon, Androutsos, Christos, Basha, Entela, Farkas, Luca, Fichna, Jakub, Janik, Piotr, Kapisyzi, Mira, Karagiannidis, Iordanis, Koumoula, Anastasia, Nagy, Peter, Puchala, Joanna, Szejko, Natalia, Szymanska, Urszula, Tsironi, Vaia, Apter, Alan, Ball, Juliane, Bodmer, Benjamin, Bognar, Emese, Buse, Judith, Vela, Marta Correa, Fremer, Carolin, Garcia-Delgar, Blanca, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Madruga-Garrido, Marcos, Pellico, Alessandra, Ruhrman, Daphna, Schnell, Jaana, Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, Turner, Victoria L., Weidinger, Elif, Alexander, John, Aranyi, Tamas, Buisman, Wim R., Buitelaar, Jan K., Driessen, Nicole, Drineas, Petros, Fan, Siyan, Forde, Natalie J., Gerasch, Sarah, van den Heuvel, Odile A., Jespersgaard, Cathrine, Kanaan, Ahmad S., Möller, Harald E., Nawaz, Muhammad S., Nespoli, Ester, Pagliaroli, Luca, Poelmans, Geert, Pouwels, Petra J.W., Rizzo, Francesca, Veltman, Dick J., van der Werf, Ysbrand D., Widomska, Joanna, Zilhäo, Nuno R., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Fernandez, Thomas V., Gilbert, Donald L., Hong, Hyun Ju, Ibanez-Gomez, Laura, Kim, Eun-Joo, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett L., Maras, Athanasios, Murphy, Tara L., Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, State, Matthew W., Visscher, Frank, Wang, Sheng, Zinner, Samuel H., Tsetsos, Fotis, Topaloudi, Apostolia, Jain, Pritesh, Yang, Zhiyu, Yu, Dongmei, Kolovos, Petros, Tumer, Zeynep, Rizzo, Renata, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Müller-Vahl, Kirsten R., Cath, Danielle C., Boomsma, Dorret I., Wolanczyk, Tomasz, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Padmanabhuni, Shanmukha S., Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Yannaki, Evangelia, Stamatoyannopoulos, John A., Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Mir, Pablo, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Roessner, Veit, Walitza, Susanne, Schrag, Anette, Martino, Davide, Tischfield, Jay A., Heiman, Gary A., Willsey, A. Jeremy, Dietrich, Andrea, Davis, Lea K., Crowley, James J., Mathews, Carol A., Scharf, Jeremiah M., Georgitsi, Marianthi, Hoekstra, Pieter J., and Paschou, Peristera

Published
2024
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4. CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions

Author

Vibert, Bethany, Segura, Patricia, Gallagher, Louise, Georgiades, Stelios, Pervanidou, Panagiota, Thurm, Audrey, Alexander, Lindsay, Anagnostou, Evdokia, Aoki, Yuta, Birken, Catherine S., Bishop, Somer L., Boi, Jessica, Bravaccio, Carmela, Brentani, Helena, Canevini, Paola, Carta, Alessandra, Charach, Alice, Costantino, Antonella, Cost, Katherine T., Cravo, Elaine A, Crosbie, Jennifer, Davico, Chiara, Donno, Federica, Fujino, Junya, Gabellone, Alessandra, Geyer, Cristiane T, Hirota, Tomoya, Kanne, Stephen, Kawashima, Makiko, Kelley, Elizabeth, Kim, Hosanna, Kim, Young Shin, Kim, So Hyun, Korczak, Daphne J., Lai, Meng-Chuan, Margari, Lucia, Marzulli, Lucia, Masi, Gabriele, Mazzone, Luigi, McGrath, Jane, Monga, Suneeta, Morosini, Paola, Nakajima, Shinichiro, Narzisi, Antonio, Nicolson, Rob, Nikolaidis, Aki, Noda, Yoshihiro, Nowell, Kerri, Polizzi, Miriam, Portolese, Joana, Riccio, Maria Pia, Saito, Manabu, Schwartz, Ida, Simhal, Anish K., Siracusano, Martina, Sotgiu, Stefano, Stroud, Jacob, Sumiya, Fernando, Tachibana, Yoshiyuki, Takahashi, Nicole, Takahashi, Riina, Tamon, Hiroki, Tancredi, Raffaella, Vitiello, Benedetto, Zuddas, Alessandro, Leventhal, Bennett, Merikangas, Kathleen, Milham, Michael P., and Di Martino, Adriana

Published
2023
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12. Prenatal Exposure to Paternal Smoking and Likelihood for Autism Spectrum Disorder

Author

Kim, Bora, Ha, Mina, Kim, Young Shin, Koh, Yun-Joo, Dong, Shan, Kwon, Ho-Jang, Kim, Young-Suk, Lim, Myung-Ho, Paik, Ki-Chung, Yoo, Seung-Jin, Kim, Hosanna, Hong, Patricia S., Sanders, Stephan J., and Leventhal, Bennett L.

Abstract

Genetics, environment, and their interactions impact autism spectrum disorder etiology. Smoking is a suspected autism spectrum disorder risk factor due to biological plausibility and high prevalence. Using two large epidemiological samples, we examined whether autism spectrum disorder was associated with prenatal paternal smoking in a Discovery sample (N = 10,245) and an independent Replication sample (N = 29,773). Paternal smoking was retrospectively assessed with questionnaires. Likelihood of having autism spectrum disorder was estimated with the Autism Spectrum Screening Questionnaire at three levels: low (<10), intermediate (10-14), and high ([greater than or equal to]15). Ordinal regression was used to examine the relationship between prenatal paternal smoking and likelihood of having autism spectrum disorder, adjusting for confounders. A total of 36.5% of Discovery sample fathers and 63.3% of Replication sample fathers smoked during the pregnancy period; 7% of the Replication sample smoker fathers smoked during the pre-conception period but quit during pregnancy period. Discovery sample prenatal paternal smoking significantly increased the likelihood of having autism spectrum disorder in their offspring (adjusted odds ratio=1.27). This was confirmed in the Replication sample with adjusted odds ratio of 1.15 among smoking pre-conception period + pregnancy period fathers; 14.4% and 11.1% increased high likelihood of autism spectrum disorder was attributable to prenatal paternal smoking in Discovery sample and Replication sample, respectively. Smoking prevention, especially in pregnancy planning, may decrease autism spectrum disorder risk in offspring.

Published
2021
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17. Investigation of gene–environment interactions in relation to tic severity

Author

Abdulkadir, Mohamed, Yu, Dongmei, Osiecki, Lisa, King, Robert A., Fernandez, Thomas V., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Garcia-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Plessen, Kerstin J., Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Visscher, Frank, Zinner, Samuel H., Mathews, Carol A., Scharf, Jeremiah M., Tischfield, Jay A., Heiman, Gary A., Dietrich, Andrea, and Hoekstra, Pieter J.

Published
2021
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21. Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder

Author

An, Joon-Yong, Lin, Kevin, Zhu, Lingxue, Werling, Donna M., Dong, Shan, Brand, Harrison, Wang, Harold Z., Zhao, Xuefang, Schwartz, Grace B., Collins, Ryan L., Currall, Benjamin B., Dastmalchi, Claudia, Dea, Jeanselle, Duhn, Clif, Gilson, Michael C., Klei, Lambertus, Liang, Lindsay, Markenscoff-Papadimitriou, Eirene, Pochareddy, Sirisha, Ahituv, Nadav, Buxbaum, Joseph D., Coon, Hilary, Daly, Mark J., Kim, Young Shin, Marth, Gabor T., Neale, Benjamin M., Quinlan, Aaron R., Rubenstein, John L., Sestan, Nenad, State, Matthew W., Willsey, A. Jeremy, Talkowski, Michael E., Devlin, Bernie, Roeder, Kathryn, and Sanders, Stephan J.

Published
2018

23. Autism Spectrum Disorder and School Bullying: Who Is the Victim? Who Is the Perpetrator?

Author

Hwang, Soonjo, Kim, Young Shin, Koh, Yun-Joo, and Leventhal, Bennett L.

Abstract

While a growing number of studies indicate associations between experiences of bullying and autism spectrum disorder (ASD), it is not clear what roles comorbid behavioral problems may play. We investigated the experiences of children with ASD as victims and/or perpetrators of bullying. Children with ASD epidemiologically ascertained participated in a cross-sectional study. Although children with ASD showed significantly increased risk for bullying involvement compared to community children, after controlling for comorbid psychopathology and other demographic factors, increased risks for being perpetrators or victim-perpetrators disappeared while risk for being bullied/teased continued to be significantly elevated. This finding will help guide medical, educational and community personnel to effectively identify children with ASD at risk for school bullying and develop interventions.

Published
2018
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25. Effect of flame‐retardant melamine and dispersants on the mechanical, thermal, and foaming properties of flexible polyurethane foam.

Author

Jeon, Yu Yeong, Jeon, Euy Sik, and Kim, Young Shin

Subjects
FOAM, URETHANE foam, DISPERSING agents, MELAMINE, FIREPROOFING, FIREPROOFING agents, MOLECULAR weights
Abstract

The objective of this study was to investigate the effect of adding flame‐retardant melamine and five different dispersants on the precipitation, foaming, mechanical, and thermal properties of flexible polyurethane foam (FPUF). Precipitation experiments were conducted to analyze the effect of dispersant on the separation of flame retardant and polyol, and the foaming characteristics of polyurethane (PU) foam after adding dispersant were analyzed. The effect of adding a dispersant on mechanical strength was characterized by measuring tensile strength, tearing strength, and hardness, and scanning electron microscopy analysis was performed to analyze morphological characteristics. Thermogravimetric analysis (TGA) was performed to analyze the thermal properties of PU foam. A horizontal flame test, limiting oxygen index test, and cone calorimeter tests were conducted to examine the flame retardancy of PU foam with flame retardant melamine and dispersant added. The dispersant ANTI‐TERRA‐U is a solution of a salt of unsaturated polyamine amides and low‐molecular acidic polyesters. And, the dispersant BYK‐220S is a solution of a low molecular weight, unsaturated acidic polycarboxylic acid polyester with a polysiloxane copolymer. The dispersants ANTI‐TERRA‐U and BYK‐220S improved the density, tensile strength, tear strength, and hardness of FPUF. TGA of the top and bottom portions of the foam showed less weight difference for samples containing dispersants, indicating better homogeneity due to improved dispersibility. Therefore, we conclude that dispersants are beneficial additives to improve the mechanical properties and dispersibility of PU foam. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Analysis of mechanical and flame‐retardant properties of flexible polyurethane foams.

Author

Kim, Young Shin and Jeon, Euy Sik

Subjects
FOAM, FIREPROOFING, URETHANE foam, MELAMINE, FIREPROOFING agents, FIRE prevention, PHOSPHATE esters, INFRARED spectroscopy
Abstract

In this study, the mechanical and flame‐retardant properties of flexible polyurethane foams (FPUF) were analyzed as a function of the type of flame retardant. FPUF containing equal amounts of two halogenated flame retardants (tris 2‐cloropropyl phosphate [TCPP] and phosphinyl alkyl phosphate ester) and three halogen‐free flame retardants (melamine, melamine cyanurate, and expandable graphite) were considered. The foaming properties of these samples were analyzed by studying the rise time and settling rate using cup foaming. Square foaming was used to analyze the mechanical properties, including density, elongation, tensile strength, and tear strength. In addition, Fourier‐transform infrared spectroscopy was performed, and flame retardancy was evaluated using a horizontal flame test and the limited oxygen index. A cone calorimeter test was also performed to evaluate the combustion characteristics. In FPUF containing the same ratio of flame retardant (15% of the total polyol), the properties of urethane foam blended with expandable graphite were improved; the tensile strength of this blend is 20% higher than that of samples containing melamine, and its peak heat release showed a 70% reduction compared to that of samples containing TCPP. These findings provide valuable reference information for developing flame retardants for fire safety FPUF in the near future. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Pre- and perinatal complications in relation to Tourette syndrome and co-occurring obsessive-compulsive disorder and attention-deficit/hyperactivity disorder

Author

Abdulkadir, Mohamed, Tischfield, Jay A., King, Robert A., Fernandez, Thomas V., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., de Bruijn, Sebastian F.T.M., Elzerman, Lonneke, Garcia-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Lamerz, Andreas, Leventhal, Bennett, Ludolph, Andrea G., Madruga-Garrido, Marcos, Maras, Athanasios, Messchendorp, Marieke D., Mir, Pablo, Morer, Astrid, Münchau, Alexander, Murphy, Tara L., Openneer, Thaïra J.C., Plessen, Kerstin J., Rath, Judith J.G., Roessner, Veit, Fründt, Odette, Shin, Eun-Young, Sival, Deborah A., Song, Dong-Ho, Song, Jungeun, Stolte, Anne-Marie, Tübing, Jennifer, van den Ban, Els, Visscher, Frank, Wanderer, Sina, Woods, Martin, Zinner, Samuel H., State, Matthew W., Heiman, Gary A., Hoekstra, Pieter J., and Dietrich, Andrea

Published
2016
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34. Autism Spectrum Disorder and School Bullying: Who is the Victim? Who is the Perpetrator?

Author

Hwang, Soonjo, Kim, Young Shin, Koh, Yun-Joo, and Leventhal, Bennett L.

Subjects
Bullying -- Risk factors -- Demographic aspects -- Research, Pervasive developmental disorders -- Complications and side effects -- Social aspects -- Research, Health
Abstract

While a growing number of studies indicate associations between experiences of bullying and autism spectrum disorder (ASD), it is not clear what roles comorbid behavioral problems may play. We investigated the experiences of children with ASD as victims and/or perpetrators of bullying. Children with ASD epidemiologically ascertained participated in a cross-sectional study. Although children with ASD showed significantly increased risk for bullying involvement compared to community children, after controlling for comorbid psychopathology and other demographic factors, increased risks for being perpetrators or victim-perpetrators disappeared while risk for being bullied/teased continued to be significantly elevated. This finding will help guide medical, educational and community personnel to effectively identify children with ASD at risk for school bullying and develop interventions., Author(s): Soonjo Hwang [sup.1] , Young Shin Kim [sup.2] [sup.3] , Yun-Joo Koh [sup.4] , Bennett L. Leventhal [sup.2] [sup.3] Author Affiliations: (1) Department of Psychiatry, University of Nebraska, 0000 [...]

Published
2018
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39. Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Author

Abdulkadir, Mohamed, Londono, Douglas, Gordon, Derek, Fernandez, Thomas V., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Elzerman, Lonneke, Fremer, Carolin, Fründt, Odette, Garcia-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Jakubovski, Ewgeni, Kim, Young Key, Kim, Young Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Ludolph, Andrea G., Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Müller-Vahl, Kirsten, Münchau, Alexander, Murphy, Tara L., Plessen, Kerstin J., Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Tübing, Jennifer, van den Ban, Els, Visscher, Frank, Wanderer, Sina, Woods, Martin, Zinner, Samuel H., King, Robert A., Tischfield, Jay A., Heiman, Gary A., Hoekstra, Pieter J., and Dietrich, Andrea

Published
2018
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43. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author

Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle C., Boomsma, Dorret I., Roessner, Veit, Wolanczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, Dietrich, Andrea, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., Paschou, Peristera, Als, Thomas D., Aschauer, Harald, Atzmon, Gil, Bækvad-Hansen, Matie, Barr, Cathy L., Barzilai, Nir, Batterson, James R., Batterson, Robert, Benarroch, Fortu, Berlin, Cheston, Boberg, Julia, Bodmer, Benjamin, Bohnenpoll, Julia, Børglum, Anders D., Brown, Lawrence W., Bruun, Ruth, Budman, Cathy L., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cheon, Keun-Ah, Chouinard, Sylvain, Coffey, Barbara J., Coppola, Giovanni, Crowley, James J., Dahl, Niklas, Darrow, Sabrina M., Daly, Mark J., De Rubeis, Silvia, Dion, Yves, Djurfeldt, Diana R., Domenech-Salgado, Laura, Eapen, Valsamma, Elzerman, Lonneke, Fernandez, Thomas V., Freimer Carolin Fremer, Nelson B., Garcia-Delgar, Blanca, Garrido, Marcos, Gilbert, Donald L., Giusti-Rodriguez, Paola, Grados, Marco, Greenberg, Erica, Grove, Jakob, Hagstrom, Julie, Halvorsen, Matt, Hansen, Bjarne, Haavik, Jan, Hebebrand, Johannes, Heiman, Gary A., Herrera, Luis, Hinney, Anke, Hirschtritt, Matthew E., Sul, Jae Hoon, Hong, Hyun Ju, Hougaard, David M., Huang, Alden Y., Ibanez-Gomez, Laura, Ivankovic, Franjo, Jankovic, Joseph, Karlsson, Elinor K., Kaprio, Jakko A., Kim, Young Key, Kim, Young-Shin, King, Robert A., Knowles, James A., Koh, Yun-Joo, Kook, Sodham, Khalifa, Najah, Konstantinidis, Anastasios, Kuperman, Samuel, Kurlan, Roger, Kvale, Gerd, Leckman, James, Lee, Paul C., Leventhal, Bennett, Lichtenstein, Paul, Lindbald-Toh, Kerstin, Lowe, Thomas, Ludolph, Andrea, da Silva, Claudia Luhrs, Luðvigsson, Pétur, Luykx, Jurjen, Lyon, Gholson J., Mahjani, Behrang, Maras, Athanasios, Mataix-Cols, David, Mattheisen, Manuel, Malaty, Irene A., McMahon, William M., McQuillin, Andrew, Meier, Sandra M., Moessner, Rainald, Mortensen, Preben B., Mors, Ole, Mudgal, Poorva, Nagy, Peter, Naarden, Allan, Neale, Benjamin M., Nawaz, Muhammad S., Nissen, Judith Becker, Nöthen Merete Nordentoft, Markus M., Nordsletten, Ashley E., Okun, Michael S., Ophoff, Roel, Osiecki, Lisa, Palotie, Aarno, Palviainen, Teemu P., Pato Michele T. Pato, Carlos N., Pittenger, Christopher, Pollak, Yehuda, Posthuma, Danielle, Ramos, Eliana, Reichert, Jennifer, Robertson, Mary M., Roffman, Joshua L., Rouleau, Guy, Rück, Christian, Sæmundsen, Evald, Samuels, Jack, Sandin, Sven, Sandor, Paul, Schlögelhofer, Monika, Shin, Eun-Young, Singer, Harvey S., Smit, Jan, Smoller, Jordan W., State, Matthew, Solem, Stian, Song, Dong-Ho, Song, Jungeun, Stamenkovic, Mara, Stefansson, Kári, Strom, Nora, Stuhrmann, Manfred, Szatkiewicz, Jin, Szymanska, Urszula, Tischfield, Jay A., Tsetsos, Fotis, Thorarensen, Ólafur, Tubing, Jennifer, Visscher, Frank, Wagner, Michael, Wanderer, Sina, Wang, Sheng, Werge, Thomas, Willsey, Jeremy A., Wolancyk, Tomasz, Woods, Douglas W., Woods, Martin, Zelaya, Ivette, Zinner, Samuel H., Apter, Alan, Ball, Juliane, Bognar, Emese, Buse, Judith, Vela, Marta Correa, Fremer, Carolin, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Madruga-Garrido, Marcos, Pellico, Alessandra, Ruhrman, Daphna, Schnell, Jaana, Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, Turner, Victoria L., Weidinger, Elif, Alexander, John, Aranyi, Tamas, Buisman, Wim R., Buitelaar, Jan K., Driessen, Nicole, Fan, Siyan, Forde, Natalie J., Gerasch, Sarah, van den Heuvel, Odile A., Jespersgaard, Cathrine, Kanaan, Ahmad S., Möller, Harald E., Nespoli, Ester, Pagliaroli, Luca, Poelmans, Geert, Pouwels, Petra J. W., Rizzo, Francesca, Veltman, Dick J., van der Werf, Ysbrand D., Widomska, Joanna, Zilhäo, Nuno R., Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Dynamic Earth and Resources, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Medizin, Autism Spectrum Disorder/genetics, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Diabetes Mellitus, Type 2, Risk Factors, Diabetes Mellitus, Tourette Syndrome/genetics, Humans, Female, Attention Deficit Disorder with Hyperactivity/genetics, Type 2, Biological Psychiatry
Abstract

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders. Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Published
2023

44. Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study.

Author

Kim, Hyun Jung, Swan, Heather, Kazmi, Sayada Zartasha, Hong, Gahwi, Kim, Young Shin, Choi, Seeun, Kang, Taeuk, Cha, Jaewoo, Eom, Jungmin, Hann, Hoo Jae, Choi, In Ah, and Ahn, Hyeong Sik

Subjects
GENETICS of rheumatoid arthritis, CONFIDENCE intervals, NATIONAL health services, COMPARATIVE studies, HEALTH insurance, RESEARCH funding, SMOKING, ODDS ratio, LONGITUDINAL method
Abstract

Objectives We evaluated the familial risk of seropositive rheumatoid arthritis (RA) and examined interactions between family history and smoking. Methods Using the National Health Insurance and Health Screening Program databases, which include information on familial relationships and lifestyle factors, we identified 5 524 403 individuals with first-degree relatives (FDRs) from 2002–2018. We calculated familial risk using hazard ratios (HRs) with 95% CIs which compare the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using the relative excess risk due to interaction (RERI). Results Individuals with affected FDR had 4.52-fold (95% CI 3.98, 5.12) increased risk of disease compared with those with unaffected FDR. Familial risk adjusted for lifestyle factors decreased slightly (HR 4.49), suggesting that a genetic contribution is the predominant driver in the familial aggregation of RA. Smoking was associated with an increased risk of disease that was more pronounced among heavy (HR 1.92 95% CI 1.70, 2.18) compared with moderate (HR 1.15 95% CI 1.04, 1.28) smoking. In the interaction analysis, the risk associated with the combined effect of smoking and family history was higher than the sum of their individual effects, though statistically non-significant (RERI 1.30 95% CI ‒0.92, 3.51). Heavy smokers with a positive family history showed a prominent interaction (RERI 4.13 95% CI ‒0.88, 9.13) which exceeded moderate smokers (RERI 0.61 95% CI ‒1.90, 3.13), suggesting a dose-response interaction pattern. Conclusion Our findings indicate the possibility of an interaction between RA-associated genes and smoking. [ABSTRACT FROM AUTHOR]

Published
2023
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