Genome-wide association scan of attention deficit hyperactivity disorder

Benjamin M Neale; Jessica Lasky-Su; Richard Anney; Barbara Franke; Kaixin Zhou; Julian B Maller; Alejandro Arias Vasquez; Philip Asherson; Wai Chen; Tobias Banaschewski; Jan Buitelaar; Richard Ebstein; Michael Gill; Ana Miranda; Robert D Oades; Herbert Roeyers; Aribert Rothenberger; Joseph Sergeant; Hans Christoph Steinhausen; Edmund Sonuga-Barke; Fernando Mulas; Eric Taylor; Nan Laird; Christoph Lange; Mark Daly; Stephen V Faraone

doi:10.1002/ajmg.b.30866

Genome-wide association scan of attention deficit hyperactivity disorder

Benjamin M Neale, Jessica Lasky-Su, Richard Anney, Barbara Franke, Kaixin Zhou, Julian B Maller, Alejandro Arias Vasquez, Philip Asherson, Wai Chen, Tobias Banaschewski, Jan Buitelaar, Richard Ebstein, Michael Gill, Ana Miranda, Robert D Oades, Herbert Roeyers, Aribert Rothenberger, Joseph Sergeant, Hans Christoph Steinhausen, Edmund Sonuga-BarkeFernando Mulas, Eric Taylor, Nan Laird, Christoph Lange, Mark Daly, Stephen V Faraone

UWA Medical School

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

204 Citations (Scopus)

Abstract

Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. We additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.

Original language	English
Pages (from-to)	1337-44
Number of pages	8
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	147B
Issue number	8
DOIs	https://doi.org/10.1002/ajmg.b.30866
Publication status	Published - 5 Dec 2008

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10.1002/ajmg.b.30866

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831205/

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Neale, B. M., Lasky-Su, J., Anney, R., Franke, B., Zhou, K., Maller, J. B., Vasquez, A. A., Asherson, P., Chen, W., Banaschewski, T., Buitelaar, J., Ebstein, R., Gill, M., Miranda, A., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J., Steinhausen, H. C., ... Faraone, S. V. (2008). Genome-wide association scan of attention deficit hyperactivity disorder. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 147B(8), 1337-44. https://doi.org/10.1002/ajmg.b.30866

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title = "Genome-wide association scan of attention deficit hyperactivity disorder",

abstract = "Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. We additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.",

keywords = "Adolescent, Algorithms, Alleles, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Child, Child, Preschool, Data Interpretation, Statistical, Genome, Human, Genome-Wide Association Study, Homozygote, Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Journal Article, Research Support, N.I.H., Extramural",

author = "Neale, {Benjamin M} and Jessica Lasky-Su and Richard Anney and Barbara Franke and Kaixin Zhou and Maller, {Julian B} and Vasquez, {Alejandro Arias} and Philip Asherson and Wai Chen and Tobias Banaschewski and Jan Buitelaar and Richard Ebstein and Michael Gill and Ana Miranda and Oades, {Robert D} and Herbert Roeyers and Aribert Rothenberger and Joseph Sergeant and Steinhausen, {Hans Christoph} and Edmund Sonuga-Barke and Fernando Mulas and Eric Taylor and Nan Laird and Christoph Lange and Mark Daly and Faraone, {Stephen V}",

year = "2008",

month = dec,

day = "5",

doi = "10.1002/ajmg.b.30866",

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

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Neale, BM, Lasky-Su, J, Anney, R, Franke, B, Zhou, K, Maller, JB, Vasquez, AA, Asherson, P, Chen, W, Banaschewski, T, Buitelaar, J, Ebstein, R, Gill, M, Miranda, A, Oades, RD, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, HC, Sonuga-Barke, E, Mulas, F, Taylor, E, Laird, N, Lange, C, Daly, M & Faraone, SV 2008, 'Genome-wide association scan of attention deficit hyperactivity disorder', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 147B, no. 8, pp. 1337-44. https://doi.org/10.1002/ajmg.b.30866

TY - JOUR

T1 - Genome-wide association scan of attention deficit hyperactivity disorder

AU - Neale, Benjamin M

AU - Lasky-Su, Jessica

AU - Anney, Richard

AU - Franke, Barbara

AU - Zhou, Kaixin

AU - Maller, Julian B

AU - Vasquez, Alejandro Arias

AU - Asherson, Philip

AU - Chen, Wai

AU - Banaschewski, Tobias

AU - Buitelaar, Jan

AU - Ebstein, Richard

AU - Gill, Michael

AU - Miranda, Ana

AU - Oades, Robert D

AU - Roeyers, Herbert

AU - Rothenberger, Aribert

AU - Sergeant, Joseph

AU - Steinhausen, Hans Christoph

AU - Sonuga-Barke, Edmund

AU - Mulas, Fernando

AU - Taylor, Eric

AU - Laird, Nan

AU - Lange, Christoph

AU - Daly, Mark

AU - Faraone, Stephen V

PY - 2008/12/5

Y1 - 2008/12/5

N2 - Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. We additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.

AB - Results of behavioral genetic and molecular genetic studies have converged to suggest that genes substantially contribute to the development of attention deficit/hyperactivity disorder (ADHD), a common disorder with an onset in childhood. Yet, despite numerous linkage and candidate gene studies, strongly consistent and replicable association has eluded detection. To search for ADHD susceptibility genes, we genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, we analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. We present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. We additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.

KW - Adolescent

KW - Algorithms

KW - Alleles

KW - Attention Deficit Disorder with Hyperactivity

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Data Interpretation, Statistical

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Homozygote

KW - Humans

KW - Linkage Disequilibrium

KW - Polymorphism, Single Nucleotide

KW - Journal Article

KW - Research Support, N.I.H., Extramural

U2 - 10.1002/ajmg.b.30866

DO - 10.1002/ajmg.b.30866

M3 - Article

C2 - 18980221

SN - 1552-4841

VL - 147B

SP - 1337

EP - 1344

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

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

IS - 8

ER -

Genome-wide association scan of attention deficit hyperactivity disorder

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