Genomic screen for substance dependence and body mass index in Southwest California Indians

Department of Molecular and Experimental Medicine, The Scripps Research Institute, USA.
Genes Brain and Behavior (Impact Factor: 3.66). 04/2007; 6(2):184-91. DOI: 10.1111/j.1601-183X.2006.00246.x
Source: PubMed


Substance abuse and obesity are health disparities that may afflict Native Americans more than some other ethnic groups. One theoretical assumption concerning Native people is that the long history of dependence on foraging and subsistence agriculture may have led to selective enrichment of traits that improve genetic fitness, so called 'thrifty' or 'fat sparing' genes. We have speculated that this same selective pressure may have enriched for genetic variants that increase the risk for consumption of alcohol and drugs of abuse. Here, we report the results of a genome scan that compared findings for two consumption phenotypes: 'any drug dependence and/or regular tobacco use' and body mass index (BMI) in southwest California (SWC) Indian families. Variance component analyses from SOLAR were used to generate log of the odds ratio (LOD) scores. Evidence for linkage was found on chromosome 6 for both the 'any drug' (LOD score = 3.3) and BMI (LOD score = 2.3) phenotypes. Bivariate analyses of the two phenotypes revealed a combined LOD score of 4.1 at that location. Additional loci on chromosomes 6, 15, 16 and 21 were found for the 'any drug' phenotype, and on chromosomes 8, 16 and 18 for BMI (LOD scores ranged between 1.2 and 2.3). These results provide suggestive evidence for linkage for substance abuse and BMI in this Mission Indian population and, furthermore, provide preliminary data suggesting that 'consumption phenotypes' may share some genetic determinants.

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    • "The prevalence of obesity in American Indians is high and is generally associated with insulin resistance and diabetes [1– 3], but generally only in the past few generations [4]. This increase in the incidence of obesity in American Indians may be due in part to the relative abundance of high fat, high calorie food, and a shift from an active to a more sedentary lifestyle [2]. "
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    ABSTRACT: Obesity is a serious public health problem, especially in some minority communities, and it has been associated with an increased risk of cardiovascular diseases. While obesity is a serious health concern in both American Indian and Mexican American populations, the relationship between obesity and cardiac autonomic control in these two populations is not well understood. The present study in a selected sample of American Indians and Mexican Americans assessed associations between obesity, blood pressure (BP), and cardiovascular autonomic control. Cardiovascular autonomic control, systolic and diastolic mean BP, and body mass index were obtained from one hundred thirty-two American Indian and Mexican American men and women who are literate in English and are residing legally in San Diego County. Men had a significant greater systolic and diastolic BP and were more likely to develop systolic prehypertension and hypertension than women. Obese participants showed greater mean heart rate (HR) and systolic and diastolic BP than nonobese participants. Obese men also exhibited greater cardiac sympathetic activity and lower cardiovagal control than obese women. These results suggest that obesity and gender differences in cardiovascular autonomic control may contribute to risk for cardiovascular disorders in this sample of American Indians and Mexican Americans.
    Cardiovascular Psychiatry and Neurology 08/2013; 2013:680687. DOI:10.1155/2013/680687
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    • "One location that provided suggestive evidence of linkage was on chromosome 12p13.33-13.32 at 5 cM that had a LOD score of 2.11. A number of previous studies in this Indian population have found evidence or suggested evidence for linkage for a number of phenotypes associated with substance dependence including alcohol dependence phenotypes (Ehlers et al., 2004b), alcohol craving (Ehlers and Wilhelmsen, 2005), tobacco usage (Ehlers and Wilhelmsen, 2006), cannabis dependence phenotypes (Ehlers et al., 2009), externalizing diagnoses (Ehlers et al., 2008a), Body Mass Index (Ehlers and Wilhelmsen, 2007), EEG phenotypes (Ehlers et al., 2010c), and level of response to alcohol (Ehlers et al., 2010d). "
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    ABSTRACT: Amphetamine-type substances are the second most widely used illicit drugs in the United States. There is evidence to suggest that stimulant use (cocaine and methamphetamine) has a heritable component, yet the areas of the genome underlying these use disorders are yet to be identified. This study's aims were to map loci linked to stimulant dependence, heavy use, and craving in an American Indian community at high risk for substance dependence. DSM diagnosis of stimulant dependence, as well as indices of stimulant "craving," and "heavy use," were obtained using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms in 381 members of multiplex families using SOLAR. Stimulant dependence, stimulant "craving," and "heavy stimulant use," were all found to be heritable. Analyses of multipoint variance component LOD scores, failed to yield evidence of linkage for stimulant dependence. For the stimulant "craving" phenotype, linkage analysis revealed a locus that had a LOD score of 3.02 on chromosome 15q25.3-26.1 near the nicotinic receptor gene cluster. A LOD score of 2.05 was found at this same site for "heavy stimulant use." Additional loci with LOD scores above 2.00 were found for stimulant "craving" on chromosomes 12p13.33-13.32 and 18q22.3. These results corroborate the importance of "craving" as an important phenotype that is associated with regions on chromosome 12, 15, and 18, that have been highlighted in prior segregation studies in this and other populations for substance dependence-related phenotypes.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 12/2011; 156B(7):772-80. DOI:10.1002/ajmg.b.31218 · 3.42 Impact Factor
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    • "This chromosomal region, which contains genes coding for the GABA A receptor subunits GABRG1, GABRA2, GABRA4, and GABRB1, was also linked to an electrophysiological phenotype (EEG beta activity) that characterizes individuals at risk for alcoholism in the COGA study (Porjesz et al., 2002), heavy drinking in the Framingham study (Wyszynski et al., 2003), cannabis dependence in the nicotine addiction genetics project (Agrawal et al., 2008), and haplotypes of " addiction phenotypes " in substance abusers (Drgon et al., 2006). Additional sites in the genome where there have been duplications of findings for linkage to alcohol and other substance dependence phenotypes within a broad support interval can be found on chromosome 2 (Reich et al., 1998; Dick et al., 2004; Ehlers et al., 2008), chromosome 5 (Hill et al., 2004; Ehlers and Wilhelmsen, 2005; Gelernter et al., 2006), chromosome 6 (Cantor and Lanning, 1999; Hill et al., 2004; Swan et al., 2006; Ehlers and Wilhelmsen, 2007), chromosome 15 (Dick et al., 2002; Ehlers et al., 2004), and chromosome 16 (Foroud et al., 1998, Ehlers et al., 2004). Strong evidence for a site on chromosome 7 has also been found by the COGA study; however, it has not as yet been duplicated by other studies (see Saccone et al., 2005; Dick et al., 2008). "
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    ABSTRACT: Evidence for genetic linkage to alcohol and other substance dependence phenotypes in areas of the human and mouse genome have now been reported with some consistency across studies. However, the question remains as to whether the genes that underlie the alcohol-related behaviors seen in mice are the same as those that underlie the behaviors observed in human alcoholics. The aims of the current set of analyses were to identify a small set of alcohol-related phenotypes in human and in mouse by which to compare quantitative trait locus (QTL) data between the species using syntenic mapping. These analyses identified that QTLs for alcohol consumption and acute and chronic alcohol withdrawal on distal mouse chromosome 1 are syntenic to a region on human chromosome 1q where a number of studies have identified QTLs for alcohol-related phenotypes. Additionally, a QTL on human chromosome 15 for alcohol dependence severity/withdrawal identified in two human studies was found to be largely syntenic with a region on mouse chromosome 9, where two groups have found QTLs for alcohol preference. In both of these cases, while the QTLs were found to be syntenic, the exact phenotypes between humans and mice did not necessarily overlap. These studies demonstrate how this technique might be useful in the search for genes underlying alcohol-related phenotypes in multiple species. However, these findings also suggest that trying to match exact phenotypes in humans and mice may not be necessary or even optimal for determining whether similar genes influence a range of alcohol-related behaviors between the two species.
    Addiction Biology 04/2010; 15(2):185-99. DOI:10.1111/j.1369-1600.2009.00195.x · 5.36 Impact Factor
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