Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
19207358
TITLE
Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerström Test for Nicotine Dependence.
ABSTRACT
AIMS NlmCategory: OBJECTIVE
A previous association analysis identified polymorphisms in gamma-aminobutyric acid receptor A, subunit 4 (GABRA4) and GABRA2 to be associated with nicotine dependence, as assessed by a score of 4 or more on the Fagerström Test for Nicotine Dependence (FTND). In the present report, we extend the previous study by expanding our genotyping efforts significantly for these two genes.
DESIGN NlmCategory: METHODS
In 1049 cases (FTND of 4 or more) and 872 controls (smokers with FTND of 0) from the United States and Australia, we examine the association between 23 GABRA4 and 39 GABRA2 recently genotyped single nucleotide polymorphisms (SNPs) and nicotine dependence using logistic regression-based association analyses using the genomic analysis package PLINK.
RESULTS NlmCategory: RESULTS
Two and 18 additional SNPs in GABRA4 and GABRA2, respectively, were associated with nicotine dependence. The SNPs identified in GABRA4 (P-value = 0.002) were restricted to introns 1 and 2, exon 1 and the 5' end of the gene, while those in GABRA2 localized to the 3' end of the gene and spanned introns 9-3, and were in moderate to high linkage disequilibrium (as measured by r(2)) with each other and with previously studied polymorphisms.
CONCLUSION NlmCategory: CONCLUSIONS
Our findings demonstrate consistently the role of GABRA4 and GABRA2 in nicotine dependence. However, further research is needed to identify the biological influence of these intronic variations and to isolate functionally relevant polymorphisms neighboring them.
DATE PUBLISHED
2009 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2009/02/12 09:00
pubmed 2009/02/12 09:00
medline 2009/05/16 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. arpana@wustl.edu
Pergadia ML Pergadia Michele L ML
Balasubramanian S Balasubramanian Sumitra S
Saccone SF Saccone Scott F SF
Hinrichs AL Hinrichs Anthony L AL
Saccone NL Saccone Nancy L NL
Breslau N Breslau Naomi N
Johnson EO Johnson Eric O EO
Hatsukami D Hatsukami Dorothy D
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Goate AM Goate Alison M AM
Rice JP Rice John P JP
Bierut LJ Bierut Laura J LJ
Madden PA Madden Pamela A F PA
INVESTIGATORS
JOURNAL
VOLUME: 104
ISSUE: 3
TITLE: Addiction (Abingdon, England)
ISOABBREVIATION: Addiction
YEAR: 2009
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1360-0443
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Addiction
COUNTRY: England
ISSNLINKING: 0965-2140
NLMUNIQUEID: 9304118
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
CA89392 NCI NIH HHS United States
DA012854 NIDA NIH HHS United States
DA019951 NIDA NIH HHS United States
DA023668 NIDA NIH HHS United States
DA21237 NIDA NIH HHS United States
HHSN271200477451C PHS HHS United States
HHSN271200477471C PHS HHS United States
K01 DA015129 NIDA NIH HHS United States
K01 DA015129-05 NIDA NIH HHS United States
K01DA015129 NIDA NIH HHS United States
K02 DA021237 NIDA NIH HHS United States
K02 DA021237-02 NIDA NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
K08 DA019951-04 NIDA NIH HHS United States
P01 CA089392 NCI NIH HHS United States
P01 CA089392-05 NCI NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 DA012854-05 NIDA NIH HHS United States
R01 DA023668 NIDA NIH HHS United States
R01 DA023668-02 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Chromosome Mapping
Chromosomes, Human, Pair 4 genetics
Exons genetics
Female genetics
Genotype genetics
Humans genetics
Introns genetics
Linkage Disequilibrium genetics
Male genetics
Middle Aged genetics
Polymorphism, Single Nucleotide genetics
Receptors, GABA-A genetics
Tobacco Use Disorder genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 GABRA2 protein, human
0 GABRA4 protein, human
0 Receptors, GABA-A
OTHER ID's
OTHERID SOURCE
NIHMS81012 NLM
PMC2653081 NLM