Genetic linkage to chromosome 22q12 for a heavy-smoking quantitative trait in two independent samples

Saccone, Scott F., Pergadia, Michele L., Loukola, Anu, Broms, Ula, Montgomery, Grant W., Wang, Jen C., Agrawal, Arpana, Dick, Danielle M., Heath, Andrew C., Todorov, Alexandre A., Maunu, Heidi, Heikkila, Kauko, Morley, Katherine I., Rice, John P., Todd, Richard D., Kaprio, Jaakko, Peltonen, Leena, Martin, Nicholas G., Goate, Alison M. and Madden, Pamela A. (2007) Genetic linkage to chromosome 22q12 for a heavy-smoking quantitative trait in two independent samples. American Journal of Human Genetics, 80 5: 856-866. doi:10.1086/513703


Author Saccone, Scott F.
Pergadia, Michele L.
Loukola, Anu
Broms, Ula
Montgomery, Grant W.
Wang, Jen C.
Agrawal, Arpana
Dick, Danielle M.
Heath, Andrew C.
Todorov, Alexandre A.
Maunu, Heidi
Heikkila, Kauko
Morley, Katherine I.
Rice, John P.
Todd, Richard D.
Kaprio, Jaakko
Peltonen, Leena
Martin, Nicholas G.
Goate, Alison M.
Madden, Pamela A.
Title Genetic linkage to chromosome 22q12 for a heavy-smoking quantitative trait in two independent samples
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2007
Sub-type Article (original research)
DOI 10.1086/513703
Volume 80
Issue 5
Start page 856
End page 866
Total pages 11
Editor C. C. Morton
K. M. DyReyes
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Subject 321011 Medical Genetics
321202 Epidemiology
321027 Respiratory Diseases
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.
Keyword Adolescent
Adult
Aged
Aged, 80 and over
Australia
Chromosomes, Human, Pair 22/*genetics
Female
Finland
Humans
*Linkage (Genetics)
Lod Score
Male
Microsatellite Repeats
Middle Aged
*Quantitative Trait Loci
Smoking/*genetics
Tobacco Use Disorder/*genetics
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
School of Psychology Publications
 
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Created: Mon, 03 Mar 2008, 11:30:04 EST