Investigation of gene–environment interactions in relation to tic severity

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

doi:https://doi.org/10.1007/s00702-021-02396-y

Investigation of gene–environment interactions in relation to tic severity

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

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.

Original language	English
Pages (from-to)	1757-1765
Number of pages	9
Journal	Journal of neural transmission (Vienna, Austria
Volume	128
Issue number	11
Early online date	2021
DOIs	https://doi.org/10.1007/s00702-021-02396-y
Publication status	Published - Nov 2021

Keywords

Gene–environment interaction
Pre- and perinatal complications
Tic severity
Tourette syndrome

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https://doi.org/10.1007/s00702-021-02396-y

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Abdulkadir, M., Yu, D., Osiecki, L., King, R. A., Fernandez, T. V., Brown, L. W., Cheon, K.-A., Coffey, B. J., Garcia-Delgar, B., Gilbert, D. L., Grice, D. E., Hagstrøm, J., Hedderly, T., Heyman, I., Hong, H. J., Huyser, C., Ibanez-Gomez, L., Kim, Y. K., Kim, Y.-S., ... Hoekstra, P. J. (2021). Investigation of gene–environment interactions in relation to tic severity. Journal of neural transmission (Vienna, Austria, 128(11), 1757-1765. https://doi.org/10.1007/s00702-021-02396-y

@article{0a7fb0ddf50f4921a1478aadf4f4ed25,

title = "Investigation of gene–environment interactions in relation to tic severity",

abstract = "Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.",

keywords = "Gene–environment interaction, Pre- and perinatal complications, Tic severity, Tourette syndrome",

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

note = "Funding Information: We wish to thank the families who have participated in and contributed to this study. We are grateful to New Jersey Center for Tourette Syndrome (NJCTS) for facilitating the inception and organization of the Tourette International Collaborative Genetics (TIC Genetics) study. We would like to thank the members of the TIC Genetics study which are: Yana Bromberg, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Li Deng, Shan Dong, Thomas V. Fernandez, Blanca Garcia-Delgar, Erika Gedvilaite, Donald L. Gilbert, Dorothy E. Grice, Julie Hagstr?m, Tammy Hedderly, Isobel Heyman,Hyun Ju Hong, Chaim Huyser, Laura Ibanez-Gomez, Young Key Kim, Young Shin Kim, Robert A. King, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett Leventhal, Marcos Madruga-Garrido, Jeffrey D. Mandell, Athanasios Maras, Pablo Mir, Astrid Morer, Alexander M?nchau, Cara Nasello, Kerstin J. Plessen, Petra Richer, Veit Roessner, Stephan Sanders, Eun-Young Shin, Louw Smith, Dong-Ho Song, Jungeun Song, Matthew W. State, Nawei Sun, Frank Visscher, Michael F. Walker, Shuoguo Wang, Jeremy Willsey, Jinchuan Xing, Yeting Zhang, Anbo Zhou, and Samuel H. Zinner. We would also wish to thank the Tourette Association of America International Consortium for Genetics (TAAICG) for providing data that was used as replication of the findings of this study. Members of the TAAICG are: Cathy L. Barr, James R. Batterson, Cheston Berlin, Ruth D. Bruun, Cathy L. Budman, Danielle C. Cath, Sylvain Chouinard, Giovanni Coppola, Nancy J. Cox, Sabrina Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Matthew E. Hirschtritt, Alden Y. Huang, Cornelia Illmann, Robert A. King, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, Carol A. Mathews, William M. MaMahon, Benjamin M. Neale, Michael S. Okun, Lisa Osiecki, David L. Pauls, Danielle Posthuma, Vasily Ramensky, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Jeremiah M. Scharf, Harvey S. Singer, Jan Smit, Jae-Hoon Sul, and Dongmei Yu. Funding Information: This research was funded by National Institute of Mental Health (NIMH) grant R01MH092293 (to GAH and JAT) and NJCTS (New Jersey Center for Tourette Syndrome and Associated Disorders; to GAH and JAT). This work was also supported by grants from the Judah Foundation, the Tourette Association of America, National Institute of Health (NIH) Grants NS40024, NS016648, MH079489, MH073250, the American Recovery and Re-investment Act (ARRA) Grants NS040024-07S1; NS16648-29S1; NS040024-09S1; MH092289; MH092290; MH092291; MH092292; R01MH092293; MH092513; MH092516; MH092520; MH071507; MH079489; MH079487; MH079488; and MH079494. Dr. Mir has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejer{\'i}a de Econom{\'i}a, Innovaci{\'o}n, Ciencia y Empresa de la Junta de Andaluc{\'i}a (CVI-02526, CTS-7685), the Consejer{\'i}a de Salud y Bienestar Social de la Junta de Andaluc{\'i}a (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurolog{\'i}a, the Fundaci{\'o}n Alicia Koplowitz, the Fundaci{\'o}n Mutua Madrile{\~n}a and the Jaques and Gloria Gossweiler Foundation. Dr. Morer has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d{\textquoteright}Innovacio (DIUE) 2009SGR1119. Dr. M{\"u}nchau has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1 and FOR 2698). This study was also supported by a Grant from the National Institute for Environmental Health Science (R01 ES021462). Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = nov,

doi = "https://doi.org/10.1007/s00702-021-02396-y",

language = "English",

volume = "128",

pages = "1757--1765",

journal = "Journal of neural transmission (Vienna, Austria",

issn = "0300-9564",

publisher = "Springer Verlag",

number = "11",

}

Abdulkadir, M, Yu, D, Osiecki, L, King, RA, Fernandez, TV, Brown, LW, Cheon, K-A, Coffey, BJ, Garcia-Delgar, B, Gilbert, DL, Grice, DE, Hagstrøm, J, Hedderly, T, Heyman, I, Hong, HJ, Huyser, C, Ibanez-Gomez, L, Kim, YK, Kim, Y-S, Koh, Y-J, Kook, S, Kuperman, S, Leventhal, B, Madruga-Garrido, M, Maras, A, Mir, P, Morer, A, Münchau, A, Plessen, KJ, Roessner, V, Shin, E-Y, Song, D-H, Song, J, Visscher, F, Zinner, SH, Mathews, CA, Scharf, JM, Tischfield, JA, Heiman, GA, Dietrich, A & Hoekstra, PJ 2021, 'Investigation of gene–environment interactions in relation to tic severity', Journal of neural transmission (Vienna, Austria, vol. 128, no. 11, pp. 1757-1765. https://doi.org/10.1007/s00702-021-02396-y

TY - JOUR

T1 - Investigation of gene–environment interactions in relation to tic severity

AU - Abdulkadir, Mohamed

AU - Yu, Dongmei

AU - Osiecki, Lisa

AU - King, Robert A.

AU - Fernandez, Thomas V.

AU - Brown, Lawrence W.

AU - Cheon, Keun-Ah

AU - Coffey, Barbara J.

AU - Garcia-Delgar, Blanca

AU - Gilbert, Donald L.

AU - Grice, Dorothy E.

AU - Hagstrøm, Julie

AU - Hedderly, Tammy

AU - Heyman, Isobel

AU - Hong, Hyun Ju

AU - Huyser, Chaim

AU - Ibanez-Gomez, Laura

AU - Kim, Young Key

AU - Kim, Young-Shin

AU - Koh, Yun-Joo

AU - Kook, Sodahm

AU - Kuperman, Samuel

AU - Leventhal, Bennett

AU - Madruga-Garrido, Marcos

AU - Maras, Athanasios

AU - Mir, Pablo

AU - Morer, Astrid

AU - Münchau, Alexander

AU - Plessen, Kerstin J.

AU - Roessner, Veit

AU - Shin, Eun-Young

AU - Song, Dong-Ho

AU - Song, Jungeun

AU - Visscher, Frank

AU - Zinner, Samuel H.

AU - Mathews, Carol A.

AU - Scharf, Jeremiah M.

AU - Tischfield, Jay A.

AU - Heiman, Gary A.

AU - Dietrich, Andrea

AU - Hoekstra, Pieter J.

N1 - Funding Information: We wish to thank the families who have participated in and contributed to this study. We are grateful to New Jersey Center for Tourette Syndrome (NJCTS) for facilitating the inception and organization of the Tourette International Collaborative Genetics (TIC Genetics) study. We would like to thank the members of the TIC Genetics study which are: Yana Bromberg, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Li Deng, Shan Dong, Thomas V. Fernandez, Blanca Garcia-Delgar, Erika Gedvilaite, Donald L. Gilbert, Dorothy E. Grice, Julie Hagstr?m, Tammy Hedderly, Isobel Heyman,Hyun Ju Hong, Chaim Huyser, Laura Ibanez-Gomez, Young Key Kim, Young Shin Kim, Robert A. King, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett Leventhal, Marcos Madruga-Garrido, Jeffrey D. Mandell, Athanasios Maras, Pablo Mir, Astrid Morer, Alexander M?nchau, Cara Nasello, Kerstin J. Plessen, Petra Richer, Veit Roessner, Stephan Sanders, Eun-Young Shin, Louw Smith, Dong-Ho Song, Jungeun Song, Matthew W. State, Nawei Sun, Frank Visscher, Michael F. Walker, Shuoguo Wang, Jeremy Willsey, Jinchuan Xing, Yeting Zhang, Anbo Zhou, and Samuel H. Zinner. We would also wish to thank the Tourette Association of America International Consortium for Genetics (TAAICG) for providing data that was used as replication of the findings of this study. Members of the TAAICG are: Cathy L. Barr, James R. Batterson, Cheston Berlin, Ruth D. Bruun, Cathy L. Budman, Danielle C. Cath, Sylvain Chouinard, Giovanni Coppola, Nancy J. Cox, Sabrina Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Matthew E. Hirschtritt, Alden Y. Huang, Cornelia Illmann, Robert A. King, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, Carol A. Mathews, William M. MaMahon, Benjamin M. Neale, Michael S. Okun, Lisa Osiecki, David L. Pauls, Danielle Posthuma, Vasily Ramensky, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Jeremiah M. Scharf, Harvey S. Singer, Jan Smit, Jae-Hoon Sul, and Dongmei Yu. Funding Information: This research was funded by National Institute of Mental Health (NIMH) grant R01MH092293 (to GAH and JAT) and NJCTS (New Jersey Center for Tourette Syndrome and Associated Disorders; to GAH and JAT). This work was also supported by grants from the Judah Foundation, the Tourette Association of America, National Institute of Health (NIH) Grants NS40024, NS016648, MH079489, MH073250, the American Recovery and Re-investment Act (ARRA) Grants NS040024-07S1; NS16648-29S1; NS040024-09S1; MH092289; MH092290; MH092291; MH092292; R01MH092293; MH092513; MH092516; MH092520; MH071507; MH079489; MH079487; MH079488; and MH079494. Dr. Mir has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña and the Jaques and Gloria Gossweiler Foundation. Dr. Morer has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. Dr. Münchau has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1 and FOR 2698). This study was also supported by a Grant from the National Institute for Environmental Health Science (R01 ES021462). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/11

Y1 - 2021/11

N2 - Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.

AB - Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.

KW - Gene–environment interaction

KW - Pre- and perinatal complications

KW - Tic severity

KW - Tourette syndrome

UR - http://www.scopus.com/inward/record.url?scp=85112353887&partnerID=8YFLogxK

U2 - https://doi.org/10.1007/s00702-021-02396-y

DO - https://doi.org/10.1007/s00702-021-02396-y

M3 - Article

C2 - 34389898

SN - 0300-9564

VL - 128

SP - 1757

EP - 1765

JO - Journal of neural transmission (Vienna, Austria

JF - Journal of neural transmission (Vienna, Austria

IS - 11

ER -

Investigation of gene–environment interactions in relation to tic severity

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