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: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

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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
Volume	128
Issue number	11
DOIs	https://doi.org/10.1007/s00702-021-02396-y
State	Published - Nov 2021

Keywords

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

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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, 128(11), 1757-1765. https://doi.org/10.1007/s00702-021-02396-y

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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 Cheon, {Keun Ah} 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 Kim, {Young Shin} and Koh, {Yun Joo} 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 Shin, {Eun Young} and Song, {Dong Ho} 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 = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = nov,

doi = "10.1007/s00702-021-02396-y",

language = "English",

volume = "128",

pages = "1757--1765",

journal = "Journal of Neural Transmission",

issn = "0300-9564",

publisher = "Springer",

number = "11",

}

Abdulkadir, M, Yu, D, Osiecki, L, King, RA, Fernandez, TV, Brown, LW, Cheon, KA, 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, YS, Koh, YJ, Kook, S, Kuperman, S, Leventhal, B, Madruga-Garrido, M, Maras, A, Mir, P, Morer, A, Münchau, A, Plessen, KJ, Roessner, V, Shin, EY, Song, DH, 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, 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.

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 - 10.1007/s00702-021-02396-y

DO - 10.1007/s00702-021-02396-y

M3 - Article

C2 - 34389898

AN - SCOPUS:85112353887

SN - 0300-9564

VL - 128

SP - 1757

EP - 1765

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

IS - 11

ER -

Investigation of gene–environment interactions in relation to tic severity

Abstract

Keywords

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