The University of Southampton
University of Southampton Institutional Repository

Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder

Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder
Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder
Here, we extended our findings from a genome-wide association study of the euphoric response to d-amphetamine in healthy human volunteers by identifying enrichment between SNPs associated with response to d-amphetamine and SNPs associated with psychiatric disorders. We found that SNPs nominally associated (P ? 0.05 and P ? 0.01) with schizophrenia and attention deficit hyperactivity disorder were also nominally associated with d-amphetamine response. Furthermore, we found that the source of this enrichment was an excess of alleles that increased sensitivity to the euphoric effects of d-amphetamine and decreased susceptibility to schizophrenia and attention deficit hyperactivity disorder. In contrast, three negative control phenotypes (height, inflammatory bowel disease, and Parkinson disease) did not show this enrichment. Taken together, our results suggest that alleles identified using an acute challenge with a dopaminergic drug in healthy individuals can be used to identify alleles that confer risk for psychiatric disorders commonly treated with dopaminergic agonists and antagonists. More importantly, our results show the use of the enrichment approach as an alternative to stringent standards for genome-wide significance and suggest a relatively novel approach to the analysis of small cohorts in which intermediate phenotypes have been measured
stimulant, dopamine hypothesis, endophenotype, GWAS, bipolar disorder
0027-8424
5968-5973
Hart, A. B.
8d9c50f8-b3b7-417f-ab04-024ff5229e94
Gamazon, E. R.
d744859d-bc17-4594-829d-3c59ca50b3cb
Engelhardt, B. E.
b33cc0a4-8a79-42c3-bf7b-28a485fff962
Sklar, P.
eb9416b7-2547-42ab-b439-032459a67bf8
Kahler, A. K.
18a167dc-6433-44bf-8f4f-a33cb06f5505
Hultman, C. M.
80905ea8-bc94-4ea0-b480-f0e5fa923555
Sullivan, P. F.
828d4562-9498-457e-83f6-87bf93d24698
Neale, B. M.
1d080401-d963-43e5-94aa-f0060bdca186
Faraone, S. V.
60d855ed-a8a8-4eca-9e62-965eb021b1e2
de Wit, H.
aaa5fff9-3df3-4be9-8304-bbed848374f6
Cox, N. J.
ec94c180-a94d-4cc1-9a44-4281c0554ff2
Palmer, A. A.
96f4f1e7-d026-4871-8266-f69d4f8f5e96
Anney, R.
d7b97910-6012-49e4-adc8-bce228fcab7f
Asherson, P.
4ecfa0c9-ea9c-47b9-aae8-429822c6c7ee
Banaschewski, T.
ca2651e5-143a-4171-b6d0-3e3853b684d8
Bayes, M.
f86d8ede-befd-4f3d-ac2d-adef7f7f2656
Biederman, J.
5d9de863-bfc1-4abc-aa3a-1078b2b91e91
Buitelaar, J. K.
421476e1-482d-4472-86e7-1450fa2e1c90
Casas, M.
1ce03190-31d7-41db-aab0-c8179c4d3d90
Cormand, B.
c0d427d6-9b98-4209-892f-2252979574e7
Crosbie, J.
3fd9acd6-8ff7-4908-9183-1052dfcbbd17
Doyle, A. E.
943eee8d-91ad-4860-8673-b3d6ade72aab
Elia, J.
12508b28-66ec-4bcb-9978-9dfad770801b
Franke, B.
d3276e6a-292a-489d-b589-de3af1b0162d
Kent, L.
ca1f2207-fa93-47fa-8d45-6c4afcd69347
Kuntsi, J.
b8f5699f-6cc2-484c-9cec-7cf741aa93ec
Lesch, K.-P.
f4dfa4a2-676c-4e26-b454-073753e35c5f
Loo, S. K.
f5820cc0-73f6-43f9-98f1-75fc0359c299
McGough, J. J.
bc308931-7750-457a-bef3-bcac92dc84ed
Medland, S. E.
0f1a2a12-b88f-4645-82ed-8c82a7fc38e6
Neale, B.
e8948089-07bd-407a-8ede-8051f536c8d1
Nelson, S. F.
02dfe0e4-5dbd-4d79-a1ce-c31c551f79d3
Oades, R. D.
490c2363-06fa-4dd6-b3e5-a2dd451e1835
Ramos-Quiroga, J. A.
61bfdc8f-b50a-444d-abb7-a4b124784ae2
Reif, A.
6a182953-a717-450a-aaca-841043d0a2d7
Ribases, M.
b75fa820-0f23-49e4-b053-15828207a7b4
Rothenberger, A.
f946fbda-7ceb-46b0-b48d-23cdaa4016aa
Schachar, R.
ab833386-d49e-41c2-9171-2f8f692a869d
Smalley, S. L.
113522fb-3423-487c-bbcc-cb537e1e7d8d
Sonuga-Barke, E.
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Steinhausen, H.-C.
f93a201f-c58f-4b6b-b6fb-3ef730edfc05
Thapar, A.
792558b3-01ec-4ccf-83c6-9f408aa3b601
Williams, N.
54385e30-6b7c-4eec-b904-bd3f9c9dedbb
Hart, A. B.
8d9c50f8-b3b7-417f-ab04-024ff5229e94
Gamazon, E. R.
d744859d-bc17-4594-829d-3c59ca50b3cb
Engelhardt, B. E.
b33cc0a4-8a79-42c3-bf7b-28a485fff962
Sklar, P.
eb9416b7-2547-42ab-b439-032459a67bf8
Kahler, A. K.
18a167dc-6433-44bf-8f4f-a33cb06f5505
Hultman, C. M.
80905ea8-bc94-4ea0-b480-f0e5fa923555
Sullivan, P. F.
828d4562-9498-457e-83f6-87bf93d24698
Neale, B. M.
1d080401-d963-43e5-94aa-f0060bdca186
Faraone, S. V.
60d855ed-a8a8-4eca-9e62-965eb021b1e2
de Wit, H.
aaa5fff9-3df3-4be9-8304-bbed848374f6
Cox, N. J.
ec94c180-a94d-4cc1-9a44-4281c0554ff2
Palmer, A. A.
96f4f1e7-d026-4871-8266-f69d4f8f5e96
Anney, R.
d7b97910-6012-49e4-adc8-bce228fcab7f
Asherson, P.
4ecfa0c9-ea9c-47b9-aae8-429822c6c7ee
Banaschewski, T.
ca2651e5-143a-4171-b6d0-3e3853b684d8
Bayes, M.
f86d8ede-befd-4f3d-ac2d-adef7f7f2656
Biederman, J.
5d9de863-bfc1-4abc-aa3a-1078b2b91e91
Buitelaar, J. K.
421476e1-482d-4472-86e7-1450fa2e1c90
Casas, M.
1ce03190-31d7-41db-aab0-c8179c4d3d90
Cormand, B.
c0d427d6-9b98-4209-892f-2252979574e7
Crosbie, J.
3fd9acd6-8ff7-4908-9183-1052dfcbbd17
Doyle, A. E.
943eee8d-91ad-4860-8673-b3d6ade72aab
Elia, J.
12508b28-66ec-4bcb-9978-9dfad770801b
Franke, B.
d3276e6a-292a-489d-b589-de3af1b0162d
Kent, L.
ca1f2207-fa93-47fa-8d45-6c4afcd69347
Kuntsi, J.
b8f5699f-6cc2-484c-9cec-7cf741aa93ec
Lesch, K.-P.
f4dfa4a2-676c-4e26-b454-073753e35c5f
Loo, S. K.
f5820cc0-73f6-43f9-98f1-75fc0359c299
McGough, J. J.
bc308931-7750-457a-bef3-bcac92dc84ed
Medland, S. E.
0f1a2a12-b88f-4645-82ed-8c82a7fc38e6
Neale, B.
e8948089-07bd-407a-8ede-8051f536c8d1
Nelson, S. F.
02dfe0e4-5dbd-4d79-a1ce-c31c551f79d3
Oades, R. D.
490c2363-06fa-4dd6-b3e5-a2dd451e1835
Ramos-Quiroga, J. A.
61bfdc8f-b50a-444d-abb7-a4b124784ae2
Reif, A.
6a182953-a717-450a-aaca-841043d0a2d7
Ribases, M.
b75fa820-0f23-49e4-b053-15828207a7b4
Rothenberger, A.
f946fbda-7ceb-46b0-b48d-23cdaa4016aa
Schachar, R.
ab833386-d49e-41c2-9171-2f8f692a869d
Smalley, S. L.
113522fb-3423-487c-bbcc-cb537e1e7d8d
Sonuga-Barke, E.
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Steinhausen, H.-C.
f93a201f-c58f-4b6b-b6fb-3ef730edfc05
Thapar, A.
792558b3-01ec-4ccf-83c6-9f408aa3b601
Williams, N.
54385e30-6b7c-4eec-b904-bd3f9c9dedbb

Hart, A. B., Gamazon, E. R. and Engelhardt, B. E. et al. (2014) Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder. Proceedings of the National Academy of Sciences, 111 (16), 5968-5973. (doi:10.1073/pnas.1318810111). (PMID:24711425)

Record type: Article

Abstract

Here, we extended our findings from a genome-wide association study of the euphoric response to d-amphetamine in healthy human volunteers by identifying enrichment between SNPs associated with response to d-amphetamine and SNPs associated with psychiatric disorders. We found that SNPs nominally associated (P ? 0.05 and P ? 0.01) with schizophrenia and attention deficit hyperactivity disorder were also nominally associated with d-amphetamine response. Furthermore, we found that the source of this enrichment was an excess of alleles that increased sensitivity to the euphoric effects of d-amphetamine and decreased susceptibility to schizophrenia and attention deficit hyperactivity disorder. In contrast, three negative control phenotypes (height, inflammatory bowel disease, and Parkinson disease) did not show this enrichment. Taken together, our results suggest that alleles identified using an acute challenge with a dopaminergic drug in healthy individuals can be used to identify alleles that confer risk for psychiatric disorders commonly treated with dopaminergic agonists and antagonists. More importantly, our results show the use of the enrichment approach as an alternative to stringent standards for genome-wide significance and suggest a relatively novel approach to the analysis of small cohorts in which intermediate phenotypes have been measured

Full text not available from this repository.

More information

e-pub ahead of print date: 7 April 2014
Published date: 22 April 2014
Keywords: stimulant, dopamine hypothesis, endophenotype, GWAS, bipolar disorder
Organisations: Clinical Neuroscience

Identifiers

Local EPrints ID: 375567
URI: https://eprints.soton.ac.uk/id/eprint/375567
ISSN: 0027-8424
PURE UUID: 44d5a749-8aef-4e7b-8bdb-f38d50de7159

Catalogue record

Date deposited: 31 Mar 2015 10:26
Last modified: 15 Jul 2019 21:25

Export record

Altmetrics

Contributors

Author: A. B. Hart
Author: E. R. Gamazon
Author: B. E. Engelhardt
Author: P. Sklar
Author: A. K. Kahler
Author: C. M. Hultman
Author: P. F. Sullivan
Author: B. M. Neale
Author: S. V. Faraone
Author: H. de Wit
Author: N. J. Cox
Author: A. A. Palmer
Author: R. Anney
Author: P. Asherson
Author: T. Banaschewski
Author: M. Bayes
Author: J. Biederman
Author: J. K. Buitelaar
Author: M. Casas
Author: B. Cormand
Author: J. Crosbie
Author: A. E. Doyle
Author: J. Elia
Author: B. Franke
Author: L. Kent
Author: J. Kuntsi
Author: K.-P. Lesch
Author: S. K. Loo
Author: J. J. McGough
Author: S. E. Medland
Author: B. Neale
Author: S. F. Nelson
Author: R. D. Oades
Author: J. A. Ramos-Quiroga
Author: A. Reif
Author: M. Ribases
Author: A. Rothenberger
Author: R. Schachar
Author: S. L. Smalley
Author: E. Sonuga-Barke
Author: H.-C. Steinhausen
Author: A. Thapar
Author: N. Williams

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×