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
17436240
TITLE
Genetic linkage to chromosome 22q12 for a heavy-smoking quantitative trait in two independent samples.
ABSTRACT
We conducted a genomewide linkage screen of a simple heavy-smoking quantitative trait, the maximum number of cigarettes smoked in a 24-h period, using two independent samples: 289 Australian and 155 Finnish nuclear multiplex families, all of which were of European ancestry and were targeted for DNA analysis by use of probands with a heavy-smoking phenotype. We analyzed the trait, using a regression of identity-by-descent allele sharing on the sum and difference of the trait values for relative pairs. Suggestive linkage was detected on chromosome 22 at 27-29 cM in each sample, with a LOD score of 5.98 at 26.96 cM in the combined sample. After additional markers were used to localize the signal, the LOD score was 5.21 at 25.46 cM. To assess the statistical significance of the LOD score in the combined sample, 1,000 simulated genomewide screens were conducted, resulting in an empirical P value of .006 for the LOD score of 5.21. This linkage signal is driven mainly by the microsatellite marker D22S315 (22.59 cM), which had a single-point LOD score of 5.41 in the combined sample and an empirical P value <.001 from 1,000 simulated genomewide screens. This marker is located within an intron of the gene ADRBK2, encoding the beta-adrenergic receptor kinase 2. Fine mapping of this linkage region may reveal variants contributing to heaviness of smoking, which will lead to a better understanding of the genetic mechanisms underlying nicotine dependence.
DATE PUBLISHED
2007 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2006/08/10
accepted 2007/02/07
aheadofprint 2007/03/26
pubmed 2007/04/17 09:00
medline 2007/06/15 09:00
entrez 2007/04/17 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Saccone SF Saccone Scott F SF Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. saccones@msnotes.wustl.edu
Pergadia ML Pergadia Michele L ML
Loukola A Loukola Anu A
Broms U Broms Ulla U
Montgomery GW Montgomery Grant W GW
Wang JC Wang Jen C JC
Agrawal A Agrawal Arpana A
Dick DM Dick Danielle M DM
Heath AC Heath Andrew C AC
Todorov AA Todorov Alexandre A AA
Maunu H Maunu Heidi H
Heikkila K Heikkila Kauko K
Morley KI Morley Katherine I KI
Rice JP Rice John P JP
Todd RD Todd Richard D RD
Kaprio J Kaprio Jaakko J
Peltonen L Peltonen Leena L
Martin NG Martin Nicholas G NG
Goate AM Goate Alison M AM
Madden PA Madden Pamela A F PA
INVESTIGATORS
JOURNAL
VOLUME: 80
ISSUE: 5
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2007
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
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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GRANTS
GRANTID AGENCY COUNTRY
AA07580 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
DA019951 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
K08 DA019951-02 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Australia
Chromosomes, Human, Pair 22 genetics
Female genetics
Finland genetics
Genetic Linkage genetics
Humans genetics
Lod Score genetics
Male genetics
Microsatellite Repeats genetics
Middle Aged genetics
Quantitative Trait Loci genetics
Smoking genetics
Tobacco Use Disorder genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC1852734 NLM
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