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
23227220
TITLE
Pathway analysis of smoking quantity in multiple GWAS identifies cholinergic and sensory pathways.
ABSTRACT
Cigarette smoking is a common addiction that increases the risk for many diseases, including lung cancer and chronic obstructive pulmonary disease. Genome-wide association studies (GWAS) have successfully identified and validated several susceptibility loci for nicotine consumption and dependence. However, the trait variance explained by these genes is only a small fraction of the estimated genetic risk. Pathway analysis complements single marker methods by including biological knowledge into the evaluation of GWAS, under the assumption that causal variants lie in functionally related genes, enabling the evaluation of a broad range of signals. Our approach to the identification of pathways enriched for multiple genes associated with smoking quantity includes the analysis of two studies and the replication of common findings in a third dataset. This study identified pathways for the cholinergic receptors, which included SNPs known to be genome-wide significant; as well as novel pathways, such as genes involved in the sensory perception of smell, that do not contain any single SNP that achieves that stringent threshold.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/06/05
accepted 2012/10/25
epublish 2012/12/05
entrez 2012/12/11 06:00
pubmed 2012/12/12 06:00
medline 2013/05/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Harari O Harari Oscar O Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, United States of America.
Wang JC Wang Jen-Chyong JC
Bucholz K Bucholz Kathleen K
Edenberg HJ Edenberg Howard J HJ
Heath A Heath Andrew A
Martin NG Martin Nicholas G NG
Pergadia ML Pergadia Michele L ML
Montgomery G Montgomery Grant G
Schrage A Schrage Andrew A
Bierut LJ Bierut Laura J LJ
Madden PF Madden Pamela F PF
Goate AM Goate Alison M AM
INVESTIGATORS
JOURNAL
VOLUME: 7
ISSUE: 12
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2012
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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ErratumIn PLoS One. 2013;8(8). doi:10.1371/annotation/21033005-e120-4364-8024-c6534b4108f6 21529783
GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
AA17688 NIAAA NIH HHS United States
DA012854 NIDA NIH HHS United States
DA019951 NIDA NIH HHS United States
DA027995 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
R01HL086694 NHLBI NIH HHS United States
R25 DA027995 NIDA NIH HHS United States
U01 HG004422 NHGRI NIH HHS United States
U01HG004438 NHGRI NIH HHS United States
UL1RR025005 NCRR NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Molecular Sequence Annotation
Receptors, Cholinergic metabolism
Reproducibility of Results metabolism
Retinoids metabolism
Sensation genetics
Signal Transduction genetics
Smell genetics
Smoking genetics
Software genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Receptors, Cholinergic
0 Retinoids
OTHER ID's
OTHERID SOURCE
PMC3515482 NLM