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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 volume 13, pages 407–416 (2008)Cite this article

Abstract

Previously, we reported a genome-wide scan for nicotine dependence (ND) in the African American (AA) sample of the Mid-South Tobacco Family (MSTF) cohort. In this study, we conducted a genome-wide scan in 629 individuals representing 200 nuclear families of European American (EA) origin of the MSTF cohort with the goals of identifying vulnerability loci for ND in the EAs and determining converging regions across the ethnic groups. We examined 385 autosomal microsatellite markers for ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerström test for ND (FTND). After performing linkage analyses using various methods implemented in the GENEHUNTER and SAGE programs, we found eight regions on chromosomes 2, 4, 9–12, 17 and 18 that met the criteria for suggestive linkage to at least one ND measure in the EA sample. Of these, the region on chromosome 4 at 43 cM showed suggestive linkage to indexed SQ, the HSI and the FTND, and the region on chromosome 9 at 24 cM showed suggestive linkage to the HSI and the FTND. To increase detection power, we analyzed a combined AA and EA sample using age, gender and ethnicity as covariates and found that the region on chromosome 12 near marker D12S372 showed significant linkage to SQ. Additionally, we found six regions on chromosomes 9–11, 13 and 18 that showed suggestive linkage to at least one ND measure in the combined sample. When we compared the linkage peaks detected for ND among the two samples and a combined sample, we found that four regions on chromosomes 9 (two regions), 11 and 18 overlapped. On the other hand, we identified five regions on chromosomes 2, 4, 10, 12 and 17 that showed linkage to ND only in the EA sample, and two regions on chromosomes 10 and 13 that showed linkage to ND only in the AA sample. For those linkages identified in only one sample, we found that the combined analysis of AA plus EA samples actually decreased the linkage signal. This indicates that some chromosomal regions may be more homogenous than others across the ethnic samples. All regions except for the one on chromosome 12 have been detected at nominally significant levels in other studies, providing independent replication of ND loci in different populations.

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Acknowledgements

We acknowledge the invaluable contributions of personal information and blood samples by all participants in the study. We thank the Center for Inherited Disease Research (CIDR) for performing microsatellite genotyping on our sample. Detailed information on genotyping methods and markers can be found at http://www.cidr.jhmi.edu. This project was funded by National Institutes of Health Grants DA-12844 to MDL and GM28356 to RCE. Some of the results of this paper were obtained using the program package SAGE, which is supported by a US Public Health Service Resource Grant (RR03655) from the National Center for Research Resources. We also thank the Rutgers University Cell and DNA Repository, the contractor for the NIDA Center for Genetic Studies, which is co-directed by Dr Jay Tischfield and Dr John Rice.

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Authors and Affiliations

  1. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA

    M D Li, X-Y Lou & D Zhang

  2. Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA

    J Z Ma

  3. ACT Center for Tobacco Treatment, Education and Research, University of Mississippi Medical Center, Jackson, MS, USA

    T J Payne

  4. Department of Criminology and Criminal Justice, University of Memphis, Memphis, TN, USA

    R T Dupont

  5. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA

    R C Elston

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Correspondence to M D Li.

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Li, M., Ma, J., Payne, T. et al. Genome-wide linkage scan for nicotine dependence in European Americans and its converging results with African Americans in the Mid-South Tobacco Family sample. Mol Psychiatry 13, 407–416 (2008). https://doi.org/10.1038/sj.mp.4002038

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