Home LiteratureArticle Details
PMID: 17436240 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

American journal of human genetics ·Vol. 80 ·No. 5 ·2007-05-00 ·Pages 856-66

Saccone SF, Pergadia ML, Loukola A, Broms U, Montgomery GW, Wang JC, Agrawal A, Dick DM, Heath AC, Todorov AA, Maunu H, Heikkila K, Morley KI, Rice JP, Todd RD, Kaprio J, Peltonen L, Martin NG, Goate AM, Madden PA

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.

MeSH Terms
Adolescent Adult Aged Aged, 80 and over Australia Chromosomes, Human, Pair 22/genetics Female Finland Genetic Linkage Humans Lod Score Male Microsatellite Repeats Middle Aged Quantitative Trait Loci Smoking/genetics Tobacco Use Disorder/genetics
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Saccone Scott F
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. [email protected]
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
Heikkila Kauko
Morley Katherine I
Rice John P
Todd Richard D
Kaprio Jaakko
Peltonen Leena
Martin Nicholas G
Goate Alison M
Madden Pamela A F
References (51)
51 references, click to expand
  1. A genome-wide search for loci contributing to smoking and alcoholism.
    Genet Epidemiol. 1999;17 Suppl 1:S55-60 PMID: 10597412
  2. Genomewide linkage scan for nicotine dependence: identification of a chromosome 5 risk locus.
    Biol Psychiatry. 2007 Jan 1;61(1):119-26 PMID: 17081504
  3. The impact of workplace smoking bans: results from a national survey.
    Tob Control. 1999 Autumn;8(3):272-7 PMID: 10599571
  4. A validity study of the SSAGA--a comparison with the SCAN.
    Addiction. 1999 Sep;94(9):1361-70 PMID: 10615721
  5. Statistical tests for detection of misspecified relationships by use of genome-screen data.
    Am J Hum Genet. 2000 Mar;66(3):1076-94 PMID: 10712219
  6. The genetics of smoking persistence in men and women: a multicultural study.
    Behav Genet. 1999 Nov;29(6):423-31 PMID: 10857247
  7. Alcoholism susceptibility loci: confirmation studies in a replicate sample and further mapping.
    Alcohol Clin Exp Res. 2000 Jul;24(7):933-45 PMID: 10923994
  8. Merlin--rapid analysis of dense genetic maps using sparse gene flow trees.
    Nat Genet. 2002 Jan;30(1):97-101 PMID: 11731797
  9. A high-resolution recombination map of the human genome.
    Nat Genet. 2002 Jul;31(3):241-7 PMID: 12053178
  10. Powerful regression-based quantitative-trait linkage analysis of general pedigrees.
    Am J Hum Genet. 2002 Aug;71(2):238-53 PMID: 12111667
  11. A note on the calculation of empirical P values from Monte Carlo procedures.
    Am J Hum Genet. 2002 Aug;71(2):439-41 PMID: 12111669
  12. The California Tobacco Control Program and potential harm reduction through reduced cigarette consumption in continuing smokers.
    Nicotine Tob Res. 2002;4 Suppl 2:S157-66 PMID: 12583355
  13. A note on calculation of empirical P values from Monte Carlo procedure.
    Am J Hum Genet. 2003 Feb;72(2):498-9 PMID: 12596795
  14. Genomic priorities and public health.
    Science. 2003 Oct 24;302(5645):599-601 PMID: 14576422
  15. A genomic scan for habitual smoking in families of alcoholics: common and specific genetic factors in substance dependence.
    Am J Med Genet A. 2004 Jan 1;124A(1):19-27 PMID: 14679582
  16. G-protein receptor kinase 3 (GRK3) influences opioid analgesic tolerance but not opioid withdrawal.
    Br J Pharmacol. 2004 Jan;141(1):55-64 PMID: 14662727
  17. Tobacco and cancer: recent epidemiological evidence.
    J Natl Cancer Inst. 2004 Jan 21;96(2):99-106 PMID: 14734699
  18. Genomic regions linked to alcohol consumption in the Framingham Heart Study.
    BMC Genet. 2003;4 Suppl 1:S101 PMID: 14975169
  19. Multiple genome-wide analyses of smoking behavior in the Framingham Heart Study.
    BMC Genet. 2003;4 Suppl 1:S102 PMID: 14975170
  20. A genome-wide scan to identify loci for smoking rate in the Framingham Heart Study population.
    BMC Genet. 2003;4 Suppl 1:S103 PMID: 14975171
  21. Genetic analysis of maximum cigarette-use phenotypes.
    BMC Genet. 2003;4 Suppl 1:S105 PMID: 14975173
  22. The nicotine dependence syndrome scale: a multidimensional measure of nicotine dependence.
    Nicotine Tob Res. 2004 Apr;6(2):327-48 PMID: 15203807
  23. Results of a genomewide linkage scan: support for chromosomes 9 and 11 loci increasing risk for cigarette smoking.
    Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):94-101 PMID: 15211640
  24. Linkage analysis of smoking initiation and quantity in Dutch sibling pairs.
    Pharmacogenomics J. 2004;4(4):274-82 PMID: 15170444
  25. Defining nicotine dependence for genetic research: evidence from Australian twins.
    Psychol Med. 2004 Jul;34(5):865-79 PMID: 15500307
  26. The investigation of linkage between a quantitative trait and a marker locus.
    Behav Genet. 1972 Mar;2(1):3-19 PMID: 4157472
  27. Mortality in relation to smoking: 20 years' observations on male British doctors.
    Br Med J. 1976 Dec 25;2(6051):1525-36 PMID: 1009386
  28. Mortality in relation to smoking: 22 years' observations on female British doctors.
    Br Med J. 1980 Apr 5;280(6219):967-71 PMID: 7417764
  29. Myocardial infarction and cigarette smoking in women younger than 50 years of age.
    JAMA. 1985 May 24-31;253(20):2965-9 PMID: 3999277
  30. A prospective study of psychological and socioeconomic characteristics, health behavior and morbidity in cigarette smokers prior to quitting compared to persistent smokers and non-smokers.
    J Clin Epidemiol. 1988;41(2):139-50 PMID: 3335880
  31. The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire.
    Br J Addict. 1991 Sep;86(9):1119-27 PMID: 1932883
  32. The CIDI-core substance abuse and dependence questions: cross-cultural and nosological issues. The WHO/ADAMHA Field Trial.
    Br J Psychiatry. 1991 Nov;159:653-8 PMID: 1756341
  33. Smoking cessation and decreased risk of stroke in women.
    JAMA. 1993 Jan 13;269(2):232-6 PMID: 8417241
  34. Genetic models for the natural history of smoking: evidence for a genetic influence on smoking persistence.
    Addict Behav. 1993 Jan-Feb;18(1):19-34 PMID: 8465673
  35. Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type.
    Am J Epidemiol. 1993 Sep 1;138(5):281-93 PMID: 8395141
  36. A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA.
    J Stud Alcohol. 1994 Mar;55(2):149-58 PMID: 8189735
  37. Accurate inference of relationships in sib-pair linkage studies.
    Am J Hum Genet. 1997 Aug;61(2):423-9 PMID: 9311748
  38. Genetic and environmental contributions to smoking.
    Addiction. 1997 Oct;92(10):1277-87 PMID: 9489045
  39. PedCheck: a program for identification of genotype incompatibilities in linkage analysis.
    Am J Hum Genet. 1998 Jul;63(1):259-66 PMID: 9634505
  40. G-protein-coupled receptors: turn-ons and turn-offs.
    Curr Opin Neurobiol. 1998 Jun;8(3):335-44 PMID: 9687355
  41. Estimation of pairwise relationships in the presence of genotyping errors.
    Am J Hum Genet. 1998 Nov;63(5):1563-4 PMID: 9792888
  42. Susceptibility genes for nicotine dependence: a genome scan and followup in an independent sample suggest that regions on chromosomes 2, 4, 10, 16, 17 and 18 merit further study.
    Mol Psychiatry. 1999 Mar;4(2):129-44 PMID: 10208445
  43. Regulation of corticotropin-releasing hormone receptor type 1alpha signaling: structural determinants for G protein-coupled receptor kinase-mediated phosphorylation and agonist-mediated desensitization.
    Mol Endocrinol. 2005 Feb;19(2):474-90 PMID: 15498832
  44. Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis.
    Pharmacogenomics J. 2005;5(3):166-72 PMID: 15724146
  45. PEDSTATS: descriptive statistics, graphics and quality assessment for gene mapping data.
    Bioinformatics. 2005 Aug 15;21(16):3445-7 PMID: 15947021
  46. Genomic screen for loci associated with tobacco usage in Mission Indians.
    BMC Med Genet. 2006;7:9 PMID: 16472381
  47. A possible smoking susceptibility locus on chromosome 11p12: evidence from sex-limitation linkage analyses in a sample of Australian twin families.
    Behav Genet. 2006 Jan;36(1):87-99 PMID: 16365831
  48. A genome-wide screen for nicotine dependence susceptibility loci.
    Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):354-60 PMID: 16671072
  49. A genomewide search finds major susceptibility loci for nicotine dependence on chromosome 10 in African Americans.
    Am J Hum Genet. 2006 Oct;79(4):745-51 PMID: 16960812
  50. A new Swedish twin registry containing environmental and medical base line data from about 14,000 same-sexed pairs born 1926-58.
    Acta Med Scand Suppl. 1976;600:1-111 PMID: 16995293
  51. Smoking behavior is under the influence of a major quantitative trait locus on human chromosome 5q.
    Genet Epidemiol. 1999;17 Suppl 1:S139-44 PMID: 10597426
Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/513703
Email
[email protected]
Published
2007-05-00
Epub
2007-00-26
Pages
856-66
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1852734
Subset
IM
Grants
NIDA NIH HHS · DA019951 · United States
NIAAA NIH HHS · AA13320 · United States
NIAAA NIH HHS · R01 AA007728 · United States
NIDA NIH HHS · DA12854 · United States
NIAAA NIH HHS · AA13321 · United States
NIDA NIH HHS · R56 DA012854 · United States
NIAAA NIH HHS · T32 AA007580 · United States
NIAAA NIH HHS · R01 AA013321 · United States
NIAAA NIH HHS · AA07728 · United States
NIDA NIH HHS · R01 DA012854 · United States
NIDA NIH HHS · K08 DA019951 · United States
NIAAA NIH HHS · AA07580 · United States
NIAAA NIH HHS · R37 AA007728 · United States
NIDA NIH HHS · K08 DA019951-02 · United States
NIAAA NIH HHS · R01 AA013320 · United States
Databases
OMIM
188890
External Links
PubMed source DOI: 10.1086/513703 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2