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
17158188
TITLE
Novel genes identified in a high-density genome wide association study for nicotine dependence.
ABSTRACT
Tobacco use is a leading contributor to disability and death worldwide, and genetic factors contribute in part to the development of nicotine dependence. To identify novel genes for which natural variation contributes to the development of nicotine dependence, we performed a comprehensive genome wide association study using nicotine dependent smokers as cases and non-dependent smokers as controls. To allow the efficient, rapid, and cost effective screen of the genome, the study was carried out using a two-stage design. In the first stage, genotyping of over 2.4 million single nucleotide polymorphisms (SNPs) was completed in case and control pools. In the second stage, we selected SNPs for individual genotyping based on the most significant allele frequency differences between cases and controls from the pooled results. Individual genotyping was performed in 1050 cases and 879 controls using 31 960 selected SNPs. The primary analysis, a logistic regression model with covariates of age, gender, genotype and gender by genotype interaction, identified 35 SNPs with P-values less than 10(-4) (minimum P-value 1.53 x 10(-6)). Although none of the individual findings is statistically significant after correcting for multiple tests, additional statistical analyses support the existence of true findings in this group. Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta3 nicotinic cholinergic receptor. This work anticipates the future directions of large-scale genome wide association studies with state-of-the-art methodological approaches and sharing of data with the scientific community.
DATE PUBLISHED
2007 Jan 1
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2006/12/07
pubmed 2006/12/13 09:00
medline 2007/04/04 09:00
entrez 2006/12/13 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Bierut LJ Bierut Laura Jean LJ Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Box 8134, St Louis, MO 63110, USA. bierut@msnotes.wustl.edu
Madden PA Madden Pamela A F PA
Breslau N Breslau Naomi N
Johnson EO Johnson Eric O EO
Hatsukami D Hatsukami Dorothy D
Pomerleau OF Pomerleau Ovide F OF
Swan GE Swan Gary E GE
Rutter J Rutter Joni J
Bertelsen S Bertelsen Sarah S
Fox L Fox Louis L
Fugman D Fugman Douglas D
Goate AM Goate Alison M AM
Hinrichs AL Hinrichs Anthony L AL
Konvicka K Konvicka Karel K
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Saccone NL Saccone Nancy L NL
Saccone SF Saccone Scott F SF
Wang JC Wang Jen C JC
Chase GA Chase Gary A GA
Rice JP Rice John P JP
Ballinger DG Ballinger Dennis G DG
INVESTIGATORS
JOURNAL
VOLUME: 16
ISSUE: 1
TITLE: Human molecular genetics
ISOABBREVIATION: Hum. Mol. Genet.
YEAR: 2007
MONTH: Jan
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0964-6906
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Hum Mol Genet
COUNTRY: England
ISSNLINKING: 0964-6906
NLMUNIQUEID: 9208958
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Hum Mol Genet. 2003 Dec 1;12(23):3133-43 14559775
Cites Eur J Hum Genet. 2002 Nov;10(11):773-81 12404112
Cites Biol Psychiatry. 2004 Jan 1;55(1):69-76 14706427
Cites Am J Hum Genet. 2004 Feb;74(2):317-25 14740319
Cites BMC Genet. 2003;4 Suppl 1:S103 14975171
Cites Psychol Med. 2004 Feb;34(2):323-33 14982138
Cites J Med Genet. 2004 Mar;41(3):e27 14985398
Cites Neuromolecular Med. 2004;5(2):133-46 15075440
Cites Am J Hum Genet. 2004 Jul;75(1):112-21 15154117
Cites MMWR Morb Mortal Wkly Rep. 2004 Jun 18;53(23):499-502 15201841
Cites Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):94-101 15211640
Cites Psychol Med. 2004 Jul;34(5):865-79 15500307
Cites Br J Addict. 1989 Jul;84(7):791-9 2758152
Cites Br J Addict. 1991 Sep;86(9):1119-27 1932883
Cites N Engl J Med. 1992 Sep 17;327(12):829-33 1508241
Cites Addict Behav. 1993 Jan-Feb;18(1):19-34 8465673
Cites Arch Gen Psychiatry. 1998 Nov;55(11):982-8 9819066
Cites Arch Gen Psychiatry. 1999 Jul;56(7):655-61 10401514
Cites Arch Gen Psychiatry. 2004 Nov;61(11):1107-15 15520358
Cites Science. 2005 Feb 18;307(5712):1072-9 15718463
Cites Am J Hum Genet. 2005 May;76(5):859-64 15759211
Cites Hum Mol Genet. 2005 May 1;14(9):1211-9 15790597
Cites MMWR Morb Mortal Wkly Rep. 2005 Jul 1;54(25):625-8 15988406
Cites J Biol Chem. 2005 Aug 19;280(33):29559-69 15972814
Cites Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11864-9 16091475
Cites Am J Physiol Lung Cell Mol Physiol. 2005 Oct;289(4):L636-46 16148052
Cites MMWR Morb Mortal Wkly Rep. 2005 Nov 11;54(44):1121-4 16280969
Cites Trends Neurosci. 2006 Jan;29(1):8-20 16337695
Cites Nat Genet. 2006 Feb;38(2):209-13 16415888
Cites Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):354-60 16671072
Cites Cell. 2006 Nov 3;127(3):621-33 17081982
Cites Genetics. 2000 Jun;155(2):945-59 10835412
Cites Behav Genet. 1999 Nov;29(6):423-31 10857247
Cites Am J Public Health. 2000 Jul;90(7):1122-7 10897192
Cites JAMA. 2000 Nov 22-29;284(20):2606-10 11086367
Cites Arch Gen Psychiatry. 2002 Aug;59(8):750-7 12150652
Cites Am J Med Genet A. 2004 Jan 1;124A(1):19-27 14679582
GRANTS
GRANTID AGENCY COUNTRY
CA89392 NCI NIH HHS United States
DA015129 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
N01DA-0-7079 NIDA NIH HHS United States
P01 CA089392 NCI NIH HHS United States
P01 CA089392-05 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Case-Control Studies
Female
Gene Frequency
Genetic Predisposition to Disease
Genome, Human
Genotype
Humans
Male
Polymorphism, Single Nucleotide
Smoking genetics
Tobacco Use Disorder genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS41082 NLM
PMC2278047 NLM