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Linkage scan of nicotine dependence in the University of California, San Francisco (UCSF) Family Alcoholism Study

  • I. R. Gizer (a1) (a2), C. L. Ehlers (a3), C. Vieten (a4), K. L. Seaton-Smith (a1), H. S. Feiler (a5), J. V. Lee (a6), S. K. Segall (a1), D. A. Gilder (a3) and K. C. Wilhelmsen (a1) (a2) (a7)...
Abstract
Background

Nicotine dependence has been shown to represent a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder though only a limited number of the findings have been replicated.

Method

In the present study, a genome-wide linkage scan for nicotine dependence was conducted in a community sample of 950 probands and 1204 relatives recruited through the University of California, San Francisco (UCSF) Family Alcoholism Study. A modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) with additional questions that probe nicotine use was used to derive DSM-IV nicotine dependence diagnoses.

Results

A locus on chromosome 2q31.1 at 184 centiMorgans nearest to marker D2S2188 yielded a logarithm (base 10) of odds (LOD) score of 3.54 (point-wise empirical p=0.000012). Additional peaks of interest were identified on chromosomes 2q13, 4p15.33-31, 11q25 and 12p11.23-21. Follow-up analyses were conducted examining the contributions of individual nicotine dependence symptoms to the chromosome 2q31.1 linkage peak as well as examining the relationship of this chromosomal region to alcohol dependence.

Conclusions

The present report suggests that chromosome 2q31.1 confers risk to the development of nicotine dependence and that this region influences a broad range of nicotine dependence symptoms rather than a specific facet of the disorder. Further, the results show that this region is not linked to alcohol dependence in this population, and thus may influence nicotine dependence specifically.

Copyright
Corresponding author
*Address for correspondence: I. R. Gizer, Ph.D., University of North Carolina at Chapel Hill, 120 Mason Farm Road, Room 5015 Genetic Medicine Building CB 7264, Chapel Hill, NC 27599-7264, USA. (Email: igizer@unc.edu)
References
Hide All
Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2002). Merlin – rapid analysis of dense genetic maps using sparse gene flow trees. Nature Genetics 30, 97–101.
Almasy L, Blangero J (1998). Multipoint quantitative-trait linkage analysis in general pedigrees. American Journal of Human Genetics 62, 11981211.
Amos CI, Krushkal J, Thiel TJ, Young A, Zhu DK, Boerwinkle E, de Andrade M (1997). Comparison of model-free linkage mapping strategies for the study of a complex trait. Genetic Epidemiology 14, 743748.
APA (1994). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. American Psychiatric Association: Washington.
Bergen AW, Korczak JF, Weissbecker KA, Goldstein AM (1999). A genome-wide search for loci contributing to smoking and alcoholism. Genetic Epidemiology 17 (Suppl.), S55S60.
Bierut LJ, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau OF, Swan GE, Rutter J, Bertelsen S, Fox L, Fugman D, Goate AM, Hinrichs AL, Konvicka K, Martin NG, Montgomery GW, Saccone NL, Saccone SF, Wang JC, Chase GA, Rice JP, Ballinger DG (2007). Novel genes identified in a high-density genome wide association study for nicotine dependence. Human Molecular Genetics 16, 2435.
Bierut LJ, Rice JP, Goate A, Hinrichs AL, Saccone NL, Foroud T, Edenberg HJ, Cloninger CR, Begleiter H, Conneally PM, Crowe RR, Hesselbrock V, Li TK, Nurnberger JI Jr., Porjesz B, Schuckit MA, Reich T (2004). A genomic scan for habitual smoking in families of alcoholics: common and specific genetic factors in substance dependence. American Journal of Medical Genetics 124A, 1927.
Bucholz KK, Cadoret R, Cloninger CR, Dinwiddie SH, Hesselbrock VM, Nurnberger JI Jr., Reich T, Schmidt I, Schuckit MA (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. Journal of Studies on Alcohol 55, 149158.
Carmelli D, Swan GE, Robinette D, Fabsitz RR (1990). Heritability of substance use in the NAS-NRC Twin Registry. Acta Geneticae Medicae et Gemellologiae (Roma) 39, 9198.
Carre N, Cauzac M, Girard J, Burnol AF (2008). Dual effect of the adapter growth factor receptor-bound protein 14 (grb14) on insulin action in primary hepatocytes. Endocrinology 149, 31093117.
Duggirala R, Almasy L, Blangero J (1999). Smoking behavior is under the influence of a major quantitative trait locus on human chromosome 5q. Genetic Epidemiology 17 (Suppl.), S139S144.
Duggirala R, Blangero J, Almasy L, Arya R, Dyer TD, Williams KL, Leach RJ, O'Connell P, Stern MP (2001). A major locus for fasting insulin concentrations and insulin resistance on chromosome 6q with strong pleiotropic effects on obesity-related phenotypes in nondiabetic Mexican Americans. American Journal of Human Genetics 68, 11491164.
Duggirala R, Williams JT, Williams-Blangero S, Blangero J (1997). A variance component approach to dichotomous trait linkage analysis using a threshold model. Genetic Epidemiology 14, 987992.
Ehlers CL, Wilhelmsen KC (2006). Genomic screen for loci associated with tobacco usage in Mission Indians. BMC Medical Genetics 7, 19.
Faraone SV, Su J, Taylor L, Wilcox M, Van Eerdewegh P, Tsuang MT (2004). A novel permutation testing method implicates sixteen nicotinic acetylcholine receptor genes as risk factors for smoking in schizophrenia families. Human Heredity 57, 5968.
Goode EL, Badzioch MD, Kim H, Gagnon F, Rozek LS, Edwards KL, Jarvik GP; Framingham Heart Study (2003). Multiple genome-wide analyses of smoking behavior in the Framingham Heart Study. BMC Genetics 4 (Suppl.), S102.
Goring HH (2002). Hlod (Homo v. 0.2) documentation. SOLAR Online User's Manual (http://solar.sfbrgenetics.org/doc/95.appendix_5.txt).
Heath AC, Madden PA (1995). Genetic influences on smoking behavior. In Behavior Genetic Approaches in Behavioral Medicine (ed. Turner J. R., Cardon L. R. and Hewitt J. K.), pp. 4566. New York: Plenum.
Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO (1991). The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. British Journal of Addiction 86, 11191127.
Jia J, Han Q, Borregaard N, Lollike K, Cygler M (2000). Crystal structure of human grancalcin, a member of the penta-EF-hand protein family. Journal of Molecular Biology 300, 12711281.
Jung J, Weeks DE, Feingold E (2006). Gene-dropping vs. empirical variance estimation for allele-sharing linkage statistics. Genetic Epidemiology 30, 652665.
Kendler KS, Myers J, Prescott CA (2007). Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Archives of General Psychiatry 64, 13131320.
Kendler KS, Neale MC, Sullivan P, Corey LA, Gardner CO, Prescott CA (1999). A population-based twin study in women of smoking initiation and nicotine dependence. Psychological Medicine 29, 299308.
Kong A, Cox NJ (1997). Allele-sharing models: LOD scores and accurate linkage tests. American Journal of Human Genetics 61, 11791188.
Lander E, Kruglyak L (1995). Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genetics 11, 241247.
Lessov CN, Martin NG, Statham DJ, Todorov AA, Slutske WS, Bucholz KK, Heath AC, Madden PAF (2004). Defining nicotine dependence for genetic research: evidence from Australian twins. Psychological Medicine 34, 865879.
Li MD (2008). Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses. Human Genetics 123, 119131.
Li MD, Cheng R, Ma JZ, Swan GE (2003). A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins. Addiction 98, 2331.
Li MD, Ma JZ, Payne TJ, Lou XY, Zhang D, Dupont RT, Elston RC (2008). Genome-wide linkage scan for nicotine dependence in European Americans and its converging results with African Americans in the Mid-South Tobacco Family sample. Molecular Psychiatry 13, 407416.
Lou XY, Ma JZ, Payne TJ, Beuten J, Crew KM, Li MD (2006). Gene-based analysis suggests association of the nicotinic acetylcholine receptor β1 subunit (CHRNB1) and M1 muscarinic acetylcholine receptor (CHRM1) with vulnerability for nicotine dependence. Human Genetics 120, 381389.
Loukola A, Broms U, Maunu H, Widen E, Heikkila K, Siivola M, Salo A, Pergadia ML, Nyman E, Sammalisto S, Perola M, Agrawal A, Heath AC, Martin NG, Madden PA, Peltonen L, Kaprio J (2008). Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background. Pharmacogenomics Journal 8, 209219.
McPeek MS, Sun L (2000). Statistical tests for detection of misspecified relationships by use of genome-screen data. American Journal of Human Genetics 66, 10761094.
Miller NS, Gold MS (1998). Comorbid cigarette and alcohol addiction: epidemiology and treatment. Journal of Addictive Diseases 17, 5566.
Mokdad AH, Marks JS, Stroup DF, Gerberding JL (2004). Actual causes of death in the United States, 2000. Journal of the American Medical Association 291, 12381245.
Morley KI, Medland SE, Ferreira MA, Lynskey MT, Montgomery GW, Heath AC, Madden PA, Martin NG (2006). A possible smoking susceptibility locus on chromosome 11p12: evidence from sex-limitation linkage analyses in a sample of Australian Twin Families. Behavior Genetics 36, 8799.
Munafö M, Clark T, Johnstone E, Murphy M, Walton R (2004). The genetic basis for smoking behavior: a systematic review and meta-analysis. Nicotine & Tobacco Research 6, 583597.
North BV, Curtis D, Sham PC (2002). A note on the calculation of empirical P values from Monte Carlo procedures. American Journal of Human Genetics 71, 439441.
Nussbaum J, Xu Q, Payne TJ, Ma JZ, Huang W, Gelernter J, Li MD (2008). Significant association of the neurexin-1 gene (NRXN1) with nicotine dependence in European- and African-American smokers. Human Molecular Genetics 17, 15691577.
O'Connell JR, Weeks DE (1998). PedCheck: a program for identification of genotype incompatibilities in linkage analysis. American Journal of Human Genetics 63, 259266.
Seaton KL, Cornell JL, Wilhelmsen KC, Vieten C (2004). Effective strategies for recruiting families ascertained through alcoholic probands. Alcoholism: Clinical and Experimental Research 28, 7884.
Sherva R, Wilhelmsen K, Pomerleau CS, Chasse SA, Rice JP, Snedecor SM, Bierut LJ, Neuman RJ, Pomerleau OF (2008). Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit α5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking. Addiction 103, 15441552.
Straub RE, Sullivan PF, Ma Y, Myakishev MV, Harris-Kerr C, Wormley B, Kadambi B, Sadek H, Silverman MA, Webb BT, Neale MC, Bulik CM, Joyce PR, Kendler KS (1999). 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. Molecular Psychiatry 4, 129144.
Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB (2004). A gene atlas of the mouse and human protein-encoding transcriptomes. Proceedings of the National Academy of Sciences USA 101, 60626067.
Sullivan PF, Kendler KS (1999). The genetic epidemiology of smoking. Nicotine & Tobacco Research 1, S51–57.
Sullivan PF, Kuo PH, Webb BT, Neale MC, Vittum J, Furberg H, Walsh D, Patterson DG, Riley B, Prescott CA, Kendler KS (2008). Genomewide linkage survey of nicotine dependence phenotypes. Drug and Alcohol Dependence 93, 210216.
Sullivan PF, Neale BM, van den Oord E, Miles MF, Neale MC, Bulik CM, Joyce PR, Straub RE, Kendler KS (2004). Candidate genes for nicotine dependence via linkage, epistasis, and bioinformatics. American Journal of Medical Genetics 126B, 2336.
Swan GE, Carmelli D, Cardon LR (1997). Heavy consumption of cigarettes, alcohol and coffee in male twins. Journal of Studies on Alcohol 58, 182190.
True WR, Xian H, Scherrer JF, Madden PA, Bucholz KK, Heath AC, Eisen SA, Lyons MJ, Goldberg J, Tsuang M (1999). Common genetic vulnerability for nicotine and alcohol dependence in men. Archives of General Psychiatry 56, 655661.
Vieten C, Seaton KL, Feiler HS, Wilhelmsen KC (2004). The University of California, San Francisco Family Alcoholism Study. I. Design, methods, and demographics. Alcoholism: Clinical and Experimental Research 28, 15091516.
Vink JM, Smit AB, de Geus EJ, Sullivan P, Willemsen G, Hottenga JJ, Smit JH, Hoogendijk WJ, Zitman FG, Peltonen L, Kaprio J, Pedersen NL, Magnusson PK, Spector TD, Kyvik KO, Morley KI, Heath AC, Martin NG, Westendorp RG, Slagboom PE, Tiemeier H, Hofman A, Uitterlinden AG, Aulchenko YS, Amin N, van Duijn C, Penninx BW, Boomsma DI (2009). Genome-wide association study of smoking initiation and current smoking. American Journal of Human Genetics 84, 367379.
Volk HE, Scherrer JF, Bucholz KK, Todorov A, Heath AC, Jacob T, True WR (2007). Evidence for specificity of transmission of alcohol and nicotine dependence in an offspring of twins design. Drug and Alcohol Dependence 87, 225232.
Wang D, Ma JZ, Li MD (2005). Mapping and verification of susceptibility loci for smoking quantity using permutation linkage analysis. Pharmacogenomics Journal 5, 166172.
Wilhelmsen KC, Schuckit M, Smith TL, Lee JV, Segall SK, Feiler HS, Kalmijn J (2003). The search for genes related to a low-level response to alcohol determined by alcohol challenges. Alcoholism: Clinical and Experimental Research 27, 10411047.
Yang HC, Chang CC, Lin CY, Chen CL, Lin CY, Fann CS (2005). A genome-wide scanning and fine mapping study of COGA data. BMC Genetics 6 (Suppl.), S30.
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