Genomic screen for loci associated with tobacco usage in Mission Indians

Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla California, USA.
BMC Medical Genetics (Impact Factor: 2.08). 02/2006; 7(1):9. DOI: 10.1186/1471-2350-7-9
Source: PubMed


The prevalence of tobacco usage in Native American adults and adolescents is higher than any other racial or ethnic group, yet biological risk and protective factors underlying tobacco use in this ethnic group remain unknown. A genome scan for loci associated with tobacco use phenotypes was performed with data collected from a community sample of Mission Indians residing in Southwest California.
A structured diagnostic interview was used to define two tobacco use phenotypes: 1) any regular tobacco usage (smoked daily for one month or more) and 2) persistent tobacco usage (smoked at least 10 cigarettes a day for more than one year). Heritability was determined and a linkage analysis was performed, using genotypes for a panel 791 microsatellite polymorphisms, for the two phenotypes using variance component methods implemented in SOLAR.
Analyses of multipoint variance component LOD scores for the two tobacco use phenotypes revealed two scores that exceeded 2.0 for the regular use phenotype: one on chromosomes 6 and one on 8. Four other loci on chromosomes 1,7,13, and 22 were found with LOD scores between 1.0 and 1.5. Two loci of interest were found on chromosomes 1 and 4 for the persistent use phenotype with LOD scores between 1.3-1.5. Bivariate linkage analysis was conducted at the site on chromosome 4 for persistent tobacco use and an alcohol drinking severity phenotype previously identified at this site. The maximum LOD score for the bivariate analysis for the region was 3.4, however, there was insufficient power to exclude coincident linkage.
While not providing evidence for linkage to specific chromosomal regions these results identify regions of interest in the genome in this Mission Indian population, for tobacco usage, some of which were identified in previous genome scans of non-native populations. Additionally, these data lend support for the hypothesis that cigarette smoking, alcohol dependence and other consumptive behaviors may share some common risk and/or protective factors in this Mission Indian population.

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    • "In the 10 years since the previous version of this chapter was written, several whole genome linkage scans in related individuals involving tobacco addiction (and/or related phenotypes, such as number of cigarettes smoked per day, maximum cigarettes ever smoked in a single day, nicotine dependence, and heaviness of smoking) have been reported in the literature (Bierut et al., 2004; Ehlers & Wilhelmsen, 2006; Gelernter et al., 2004, 2007; Goode et al., 2003; M. Li et al., 2006; Loukola et al., 2008; Morley et al., 2006; S. Saccone, Hinrichs, et al., 2007; Straub et al., 1999; Swan et al., 2006; Vink et al., 2004). One study identified suggestive linkage peaks on chromosome 6 (near the location of OPRM1 , the gene encoding for the mu-opioid receptor) for scores from the Fagerström Test for Nicotine Dependence (FTND; Heatherton, Kozlowski, Frecker, & Fagerström, 1991) and total withdrawal severity (Swan et al., 2006). "

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    • "Nonetheless, previous family-based samples selected for alcohol dependence have identified genetic loci that confer risk to alcohol and tobacco use phenotypes. For example, loci on chromosomes 2 (Bierut et al., 2004), 4 (Ehlers and Wilhelmsen, 2006), 7 (Loukola et al., 2008; Sullivan et al., 2008), and 18 (Sullivan et al., 2008) have been shown to contribute jointly to alcohol and nicotine dependence The lack of such findings in the present study suggest that unique genetic influences contributed to nicotine and alcohol dependence in the UCSF Family Alcoholism Study. "
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    • "While twin-studies can help to elucidate the extent to which an observed behavior is heritable, genomic research approaches can begin to identify chromosomal regions or specific genes associated with the behavioral phenotype (e.g., nicotine withdrawal). To date, linkage studies using smoking-related phenotypes have included behaviors such as smoking initiation (Bergen et al., 2003; Ehlers and Wilhelmsen, 2006; Morley et al., 2006; Vink et al., 2004), quantity smoked (Swan et al., 2006; Morley et al., 2006; Bergen et al., 1999; Duggirala et al., 1999; Goode et al., 2003; Li et al., 2003; Li et al., 2006; Saccone et al., 2003; Wang et al., 2005), habitual smoking (Ehlers and Wilhelmsen, 2006; Bierut et al., 2004; Gelernter et al., 2004), nicotine dependence (FTND: Swan et al., 2006; Li et al., 2006; Gelernter et al., 2007; Straub et al., 1999; DSM-IV: Swan et al., 2006; Gelernter et al., 2007), short-term cessation (Swan et al., 2006), and maximum cigarettes smoked in a 24- hour period (Saccone et al., 2007a). Suggestive linkage has been reported at multiple locations across the genome, but with most LOD scores not exceeding 3.0 and indeed most samples used were not selected for informativeness for cigarette smoking, with a few notable exceptions: 1) quantity smoked: LOD = 4.17 on chromosome 10 (Li et al., 2006), 2) short-term cessation: LOD = 4.0 on chromosome 16 (Swan et al., 2006), and 3) maximum cigarettes consumed in 24-hours: LOD = 5.98 on chromosome 22 (Saccone et al., 2007a). "
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