Case-control genome-wide association study of attention-deficit/ hyperactivity disorder

Benjamin M Neale, Sarah E Medland, Stephan Ripke, Richard J Anney, Philip J Asherson, Jan K Buitelaar, Barbara Franke, Michael Gill, Lindsey S W Kent, Peter A Holmans, Frank A Middleton, Anita Thapar, Klaus Peter Lesch, Stephen V Faraone, Mark J Daly, Thuy Trang Nguyen, Helmut H Schafer, Hans Christoph Steinhausen, Andreas Reif, Tobias J Renner & 13 others Marcel Romanos, Jasmin Romanos, Andreas Warnke, Susanne Walitza, Christine Margarete Freitag, Jobst D Meyer, Haukur Orvar Palmason, Aribert Rothenberger, Ziarih Hawi, Joseph A Sergeant, Herbert Roeyers, Eric O Mick, Joseph J Biederman

Research output: Contribution to journalArticleResearchpeer-review

115 Citations (Scopus)

Abstract

Objective: Although twin and family studies have shown attention-deficit/ hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model. Results: No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1. Conclusions: The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles
Original languageEnglish
Pages (from-to)906 - 920
Number of pages15
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume49
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

Cite this

Neale, B. M., Medland, S. E., Ripke, S., Anney, R. J., Asherson, P. J., Buitelaar, J. K., ... Biederman, J. J. (2010). Case-control genome-wide association study of attention-deficit/ hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 49(9), 906 - 920. https://doi.org/10.1016/j.jaac.2010.06.007
Neale, Benjamin M ; Medland, Sarah E ; Ripke, Stephan ; Anney, Richard J ; Asherson, Philip J ; Buitelaar, Jan K ; Franke, Barbara ; Gill, Michael ; Kent, Lindsey S W ; Holmans, Peter A ; Middleton, Frank A ; Thapar, Anita ; Lesch, Klaus Peter ; Faraone, Stephen V ; Daly, Mark J ; Nguyen, Thuy Trang ; Schafer, Helmut H ; Steinhausen, Hans Christoph ; Reif, Andreas ; Renner, Tobias J ; Romanos, Marcel ; Romanos, Jasmin ; Warnke, Andreas ; Walitza, Susanne ; Freitag, Christine Margarete ; Meyer, Jobst D ; Palmason, Haukur Orvar ; Rothenberger, Aribert ; Hawi, Ziarih ; Sergeant, Joseph A ; Roeyers, Herbert ; Mick, Eric O ; Biederman, Joseph J. / Case-control genome-wide association study of attention-deficit/ hyperactivity disorder. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2010 ; Vol. 49, No. 9. pp. 906 - 920.
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title = "Case-control genome-wide association study of attention-deficit/ hyperactivity disorder",
abstract = "Objective: Although twin and family studies have shown attention-deficit/ hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model. Results: No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1. Conclusions: The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles",
author = "Neale, {Benjamin M} and Medland, {Sarah E} and Stephan Ripke and Anney, {Richard J} and Asherson, {Philip J} and Buitelaar, {Jan K} and Barbara Franke and Michael Gill and Kent, {Lindsey S W} and Holmans, {Peter A} and Middleton, {Frank A} and Anita Thapar and Lesch, {Klaus Peter} and Faraone, {Stephen V} and Daly, {Mark J} and Nguyen, {Thuy Trang} and Schafer, {Helmut H} and Steinhausen, {Hans Christoph} and Andreas Reif and Renner, {Tobias J} and Marcel Romanos and Jasmin Romanos and Andreas Warnke and Susanne Walitza and Freitag, {Christine Margarete} and Meyer, {Jobst D} and Palmason, {Haukur Orvar} and Aribert Rothenberger and Ziarih Hawi and Sergeant, {Joseph A} and Herbert Roeyers and Mick, {Eric O} and Biederman, {Joseph J}",
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Neale, BM, Medland, SE, Ripke, S, Anney, RJ, Asherson, PJ, Buitelaar, JK, Franke, B, Gill, M, Kent, LSW, Holmans, PA, Middleton, FA, Thapar, A, Lesch, KP, Faraone, SV, Daly, MJ, Nguyen, TT, Schafer, HH, Steinhausen, HC, Reif, A, Renner, TJ, Romanos, M, Romanos, J, Warnke, A, Walitza, S, Freitag, CM, Meyer, JD, Palmason, HO, Rothenberger, A, Hawi, Z, Sergeant, JA, Roeyers, H, Mick, EO & Biederman, JJ 2010, 'Case-control genome-wide association study of attention-deficit/ hyperactivity disorder', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 49, no. 9, pp. 906 - 920. https://doi.org/10.1016/j.jaac.2010.06.007

Case-control genome-wide association study of attention-deficit/ hyperactivity disorder. / Neale, Benjamin M; Medland, Sarah E; Ripke, Stephan; Anney, Richard J; Asherson, Philip J; Buitelaar, Jan K; Franke, Barbara; Gill, Michael; Kent, Lindsey S W; Holmans, Peter A; Middleton, Frank A; Thapar, Anita; Lesch, Klaus Peter; Faraone, Stephen V; Daly, Mark J; Nguyen, Thuy Trang; Schafer, Helmut H; Steinhausen, Hans Christoph; Reif, Andreas; Renner, Tobias J; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine Margarete; Meyer, Jobst D; Palmason, Haukur Orvar; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph A; Roeyers, Herbert; Mick, Eric O; Biederman, Joseph J.

In: Journal of the American Academy of Child and Adolescent Psychiatry, Vol. 49, No. 9, 2010, p. 906 - 920.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Case-control genome-wide association study of attention-deficit/ hyperactivity disorder

AU - Neale, Benjamin M

AU - Medland, Sarah E

AU - Ripke, Stephan

AU - Anney, Richard J

AU - Asherson, Philip J

AU - Buitelaar, Jan K

AU - Franke, Barbara

AU - Gill, Michael

AU - Kent, Lindsey S W

AU - Holmans, Peter A

AU - Middleton, Frank A

AU - Thapar, Anita

AU - Lesch, Klaus Peter

AU - Faraone, Stephen V

AU - Daly, Mark J

AU - Nguyen, Thuy Trang

AU - Schafer, Helmut H

AU - Steinhausen, Hans Christoph

AU - Reif, Andreas

AU - Renner, Tobias J

AU - Romanos, Marcel

AU - Romanos, Jasmin

AU - Warnke, Andreas

AU - Walitza, Susanne

AU - Freitag, Christine Margarete

AU - Meyer, Jobst D

AU - Palmason, Haukur Orvar

AU - Rothenberger, Aribert

AU - Hawi, Ziarih

AU - Sergeant, Joseph A

AU - Roeyers, Herbert

AU - Mick, Eric O

AU - Biederman, Joseph J

PY - 2010

Y1 - 2010

N2 - Objective: Although twin and family studies have shown attention-deficit/ hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model. Results: No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1. Conclusions: The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles

AB - Objective: Although twin and family studies have shown attention-deficit/ hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genomewide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases with DSM-IV ADHD genotyped using the Affymetrix 5.0 array and 2,455 repository controls screened for psychotic and bipolar symptoms genotyped using Affymetrix 6.0 arrays. A consensus SNP set was imputed using BEAGLE 3.0, resulting in an analysis dataset of 1,033,244 SNPs. Data were analyzed using a generalized linear model. Results: No genome-wide significant associations were found. The most significant results implicated the following genes: PRKG1, FLNC, TCERG1L, PPM1H, NXPH1, PPM1H, CDH13, HK1, and HKDC1. Conclusions: The current analyses are a useful addition to the present literature and will make a valuable contribution to future meta-analyses. The candidate gene findings are consistent with a prior meta-analysis in suggesting that the effects of ADHD risk variants must, individually, be very small and/or include multiple rare alleles

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928577/pdf/nihms-215285.pdf

U2 - 10.1016/j.jaac.2010.06.007

DO - 10.1016/j.jaac.2010.06.007

M3 - Article

VL - 49

SP - 906

EP - 920

JO - Journal of the American Academy of Child and Adolescent Psychiatry

JF - Journal of the American Academy of Child and Adolescent Psychiatry

SN - 0890-8567

IS - 9

ER -