Genetic Linkage to Chromosome 22q12 for a Heavy-Smoking Quantitative Trait in Two Independent Samples

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...

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Bibliographic Details
Published in:American journal of human genetics 2007-05, Vol.80 (5), p.856-866
Main Authors: Saccone, Scott F., Pergadia, Michele L., Loukola, Anu, Broms, Ulla, Montgomery, Grant W., Wang, Jen C., Agrawal, Arpana, Dick, Danielle M., Heath, Andrew C., Todorov, Alexandre A., Maunu, Heidi, Heikkilä, Kauko, Morley, Katherine I., Rice, John P., Todd, Richard D., Kaprio, Jaakko, Peltonen, Leena, Martin, Nicholas G., Goate, Alison M., Madden, Pamela A.F.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Australia
Biological and medical sciences
Chromosomes
Chromosomes, Human, Pair 22 - genetics
Female
Finland
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genetic Linkage
Genetics of eukaryotes. Biological and molecular evolution
Genomics
Genotype & phenotype
Humans
Lod Score
Male
Medical genetics
Medical sciences
Microsatellite Repeats
Middle Aged
Molecular and cellular biology
Quantitative Trait Loci
Regression analysis
Smoking
Smoking - genetics
Tobacco Use Disorder - genetics
Tobacco, tobacco smoking
Toxicology
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Summary: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
ISSN:0002-9297
1537-6605
DOI:10.1086/513703