Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes

Naomi Lowe; Aiveen Kirley; Ziarih Hawi; Pak Sham; Harvey Wickham; Christopher J. Kratochvil; Shelley D. Smith; Saretta Y. Lee; Florence Levy; Lindsey Kent; Fiona Middle; Luis A. Rohde; Tatiana Roman; Eda Tahir; Yanke Yazgan; Philip Asherson; Jonathan Mil; Anita Thapar; Antony Payton; Richard D. Todd; Timothy Stephens; Richard P. Ebstein; Iris Manor; Cathy L. Barr; Karen G. Wigg; Richard J. Sinke; Jan K. Buitelaar; Susan L. Smalley; Stan F. Nelson; Joseph Biederman; Stephen V. Faraone; Michael Gill

doi:10.1086/381561

Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes

Naomi Lowe, Aiveen Kirley, Ziarih Hawi, Pak Sham, Harvey Wickham, Christopher J. Kratochvil, Shelley D. Smith, Saretta Y. Lee, Florence Levy, Lindsey Kent, Fiona Middle, Luis A. Rohde, Tatiana Roman, Eda Tahir, Yanke Yazgan, Philip Asherson, Jonathan Mil, Anita Thapar, Antony Payton, Richard D. ToddTimothy Stephens, Richard P. Ebstein, Iris Manor, Cathy L. Barr, Karen G. Wigg, Richard J. Sinke, Jan K. Buitelaar, Susan L. Smalley, Stan F. Nelson, Joseph Biederman, Stephen V. Faraone, Michael Gill

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

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)n repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P = .00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Original language	English
Pages (from-to)	348-356
Number of pages	8
Journal	American Journal of Human Genetics
Volume	74
Issue number	2
DOIs	https://doi.org/10.1086/381561
Publication status	Published - Feb 2004

Keywords

classification: Attention Deficit Disorder with Hyperactivity
Female
Genetic Markers
Humans
Male
Odds Ratio
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

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10.1086/381561

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Lowe, N., Kirley, A., Hawi, Z., Sham, P., Wickham, H., Kratochvil, C. J., Smith, S. D., Lee, S. Y., Levy, F., Kent, L., Middle, F., Rohde, L. A., Roman, T., Tahir, E., Yazgan, Y., Asherson, P., Mil, J., Thapar, A., Payton, A., ... Gill, M. (2004). Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes. American Journal of Human Genetics, 74(2), 348-356. https://doi.org/10.1086/381561

@article{fbf92e2060df4ff791b29bc814d783f3,

title = "Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes",

abstract = "Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)n repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P = .00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.",

keywords = "classification: Attention Deficit Disorder with Hyperactivity, Female, Genetic Markers, Humans, Male, Odds Ratio, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.",

author = "Naomi Lowe and Aiveen Kirley and Ziarih Hawi and Pak Sham and Harvey Wickham and Kratochvil, {Christopher J.} and Smith, {Shelley D.} and Lee, {Saretta Y.} and Florence Levy and Lindsey Kent and Fiona Middle and Rohde, {Luis A.} and Tatiana Roman and Eda Tahir and Yanke Yazgan and Philip Asherson and Jonathan Mil and Anita Thapar and Antony Payton and Todd, {Richard D.} and Timothy Stephens and Ebstein, {Richard P.} and Iris Manor and Barr, {Cathy L.} and Wigg, {Karen G.} and Sinke, {Richard J.} and Buitelaar, {Jan K.} and Smalley, {Susan L.} and Nelson, {Stan F.} and Joseph Biederman and Faraone, {Stephen V.} and Michael Gill",

year = "2004",

month = feb,

doi = "10.1086/381561",

language = "English",

volume = "74",

pages = "348--356",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "2",

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Lowe, N, Kirley, A, Hawi, Z, Sham, P, Wickham, H, Kratochvil, CJ, Smith, SD, Lee, SY, Levy, F, Kent, L, Middle, F, Rohde, LA, Roman, T, Tahir, E, Yazgan, Y, Asherson, P, Mil, J, Thapar, A, Payton, A, Todd, RD, Stephens, T, Ebstein, RP, Manor, I, Barr, CL, Wigg, KG, Sinke, RJ, Buitelaar, JK, Smalley, SL, Nelson, SF, Biederman, J, Faraone, SV & Gill, M 2004, 'Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes', American Journal of Human Genetics, vol. 74, no. 2, pp. 348-356. https://doi.org/10.1086/381561

TY - JOUR

T1 - Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes

AU - Lowe, Naomi

AU - Kirley, Aiveen

AU - Hawi, Ziarih

AU - Sham, Pak

AU - Wickham, Harvey

AU - Kratochvil, Christopher J.

AU - Smith, Shelley D.

AU - Lee, Saretta Y.

AU - Levy, Florence

AU - Kent, Lindsey

AU - Middle, Fiona

AU - Rohde, Luis A.

AU - Roman, Tatiana

AU - Tahir, Eda

AU - Yazgan, Yanke

AU - Asherson, Philip

AU - Mil, Jonathan

AU - Thapar, Anita

AU - Payton, Antony

AU - Todd, Richard D.

AU - Stephens, Timothy

AU - Ebstein, Richard P.

AU - Manor, Iris

AU - Barr, Cathy L.

AU - Wigg, Karen G.

AU - Sinke, Richard J.

AU - Buitelaar, Jan K.

AU - Smalley, Susan L.

AU - Nelson, Stan F.

AU - Biederman, Joseph

AU - Faraone, Stephen V.

AU - Gill, Michael

PY - 2004/2

Y1 - 2004/2

N2 - Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)n repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P = .00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

AB - Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)n repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P = .00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

KW - classification: Attention Deficit Disorder with Hyperactivity

KW - Female

KW - Genetic Markers

KW - Humans

KW - Male

KW - Odds Ratio

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1086/381561

DO - 10.1086/381561

M3 - Article

SN - 0002-9297

VL - 74

SP - 348

EP - 356

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 2

ER -

Joint Analysis of the DRD5 Marker Concludes Association with Attention-Deficit/Hyperactivity Disorder Confined to the Predominantly Inattentive and Combined Subtypes

Abstract

Keywords

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