Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan

Edmund J. S. Sonuga-Barke; Jessica Lasky-Su; Benjamin M. Neale; Robert Oades; Wai Chen; Barbara Franke; Jan Buitelaar; Tobias Banaschewski; Richard Ebstein; Michael Gill; Richard Anney; Ana Miranda; Fernando Mulas; Herbert Roeyers; Aribert Rothenberger; Joseph Sergeant; Hans Christoph Steinhausen; Margaret Thompson; Philip Asherson; Stephen V. Faraone

doi:10.1002/ajmg.b.30860

Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan

Edmund J. S. Sonuga-Barke, Jessica Lasky-Su, Benjamin M. Neale, Robert Oades, Wai Chen, Barbara Franke, Jan Buitelaar, Tobias Banaschewski, Richard Ebstein, Michael Gill, Richard Anney, Ana Miranda, Fernando Mulas, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Hans Christoph Steinhausen, Margaret Thompson, Philip Asherson, Stephen V. Faraone

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

79 Citations (Scopus)

Abstract

Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-Aide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were <10(-5) implicating both novel genes as well as some previously supported candidates. These were found equally often for all of the interactions being investigated. The observed interactions in SLC1A1 and NRG3 SNPs represent reasonable candidate genes for further investigation given their previous association with several psychiatric illnesses. We find evidence for the role of EE in moderating the effects of genes on ADHD severity and comorbid conduct disorder, implicating both novel and established candidates. These findings need replicating in larger independent samples. (c) 2008 Wiley-Liss, Inc.

Original language	English
Pages (from-to)	1359 - 1368
Number of pages	10
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	147B
Issue number	8
DOIs	https://doi.org/10.1002/ajmg.b.30860
Publication status	Published - 5 Dec 2008

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Sonuga-Barke, E. J. S., Lasky-Su, J., Neale, B. M., Oades, R., Chen, W., Franke, B., Buitelaar, J., Banaschewski, T., Ebstein, R., Gill, M., Anney, R., Miranda, A., Mulas, F., Roeyers, H., Rothenberger, A., Sergeant, J., Steinhausen, H. C., Thompson, M., Asherson, P., & Faraone, S. V. (2008). Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 147B(8), 1359 - 1368. https://doi.org/10.1002/ajmg.b.30860

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title = "Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan",

abstract = "Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-Aide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were <10(-5) implicating both novel genes as well as some previously supported candidates. These were found equally often for all of the interactions being investigated. The observed interactions in SLC1A1 and NRG3 SNPs represent reasonable candidate genes for further investigation given their previous association with several psychiatric illnesses. We find evidence for the role of EE in moderating the effects of genes on ADHD severity and comorbid conduct disorder, implicating both novel and established candidates. These findings need replicating in larger independent samples. (c) 2008 Wiley-Liss, Inc.",

author = "Sonuga-Barke, {Edmund J. S.} and Jessica Lasky-Su and Neale, {Benjamin M.} and Robert Oades and Wai Chen and Barbara Franke and Jan Buitelaar and Tobias Banaschewski and Richard Ebstein and Michael Gill and Richard Anney and Ana Miranda and Fernando Mulas and Herbert Roeyers and Aribert Rothenberger and Joseph Sergeant and Steinhausen, {Hans Christoph} and Margaret Thompson and Philip Asherson and Faraone, {Stephen V.}",

year = "2008",

month = dec,

day = "5",

doi = "10.1002/ajmg.b.30860",

language = "English",

volume = "147B",

pages = "1359 -- 1368",

journal = "American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics",

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Sonuga-Barke, EJS, Lasky-Su, J, Neale, BM, Oades, R, Chen, W, Franke, B, Buitelaar, J, Banaschewski, T, Ebstein, R, Gill, M, Anney, R, Miranda, A, Mulas, F, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, HC, Thompson, M, Asherson, P & Faraone, SV 2008, 'Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 147B, no. 8, pp. 1359 - 1368. https://doi.org/10.1002/ajmg.b.30860

Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan. / Sonuga-Barke, Edmund J. S.; Lasky-Su, Jessica; Neale, Benjamin M. et al.
In: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Vol. 147B, No. 8, 05.12.2008, p. 1359 - 1368.

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

TY - JOUR

T1 - Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan

AU - Sonuga-Barke, Edmund J. S.

AU - Lasky-Su, Jessica

AU - Neale, Benjamin M.

AU - Oades, Robert

AU - Chen, Wai

AU - Franke, Barbara

AU - Buitelaar, Jan

AU - Banaschewski, Tobias

AU - Ebstein, Richard

AU - Gill, Michael

AU - Anney, Richard

AU - Miranda, Ana

AU - Mulas, Fernando

AU - Roeyers, Herbert

AU - Rothenberger, Aribert

AU - Sergeant, Joseph

AU - Steinhausen, Hans Christoph

AU - Thompson, Margaret

AU - Asherson, Philip

AU - Faraone, Stephen V.

PY - 2008/12/5

Y1 - 2008/12/5

N2 - Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-Aide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were <10(-5) implicating both novel genes as well as some previously supported candidates. These were found equally often for all of the interactions being investigated. The observed interactions in SLC1A1 and NRG3 SNPs represent reasonable candidate genes for further investigation given their previous association with several psychiatric illnesses. We find evidence for the role of EE in moderating the effects of genes on ADHD severity and comorbid conduct disorder, implicating both novel and established candidates. These findings need replicating in larger independent samples. (c) 2008 Wiley-Liss, Inc.

AB - Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Childhood Symptoms interview. Maternal criticism and warmth (i.e., EE) were coded by independent observers on comments made during the interview. No G x E interactions reached genome-Aide significance. Nominal effects were found both with and without genetic main effects. For those with genetic main effects 36 uncorrected interaction P-values were <10(-5) implicating both novel genes as well as some previously supported candidates. These were found equally often for all of the interactions being investigated. The observed interactions in SLC1A1 and NRG3 SNPs represent reasonable candidate genes for further investigation given their previous association with several psychiatric illnesses. We find evidence for the role of EE in moderating the effects of genes on ADHD severity and comorbid conduct disorder, implicating both novel and established candidates. These findings need replicating in larger independent samples. (c) 2008 Wiley-Liss, Inc.

U2 - 10.1002/ajmg.b.30860

DO - 10.1002/ajmg.b.30860

M3 - Article

SN - 1552-485X

VL - 147B

SP - 1359

EP - 1368

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

IS - 8

ER -

Does Parental Expressed Emotion Moderate Genetic Effects in ADHD? An Exploration Using a Genome Wide Association Scan

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