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Significant Genetic Component (significant + genetic_component)
Selected AbstractsGenetic and Other Contributions to Alcohol Intake in Rhesus Macaques (Macaca mulatta)ALCOHOLISM, Issue 3 2006Joseph G. Lorenz Background: The etiology of alcoholism and alcohol abuse, like many other complex diseases, is heterogeneous and multifactorial. Numerous studies demonstrate a genetic contribution to variation in the expression of alcohol-related disorders in humans. Over the past decade, nonhuman primates have emerged as a valuable model for some aspects of human alcohol abuse because of their phylogenetic proximity to humans. Long-term, longitudinal studies of rhesus macaques (Macaca mulatta) have provided much insight into environmental influences, especially early life experiences, on alcohol consumption and behavior patterns that characterize alcohol intake later in life. It is not known, however, whether there is a genetic component as well to the variation seen in alcohol consumption in rhesus macaques. A significant genetic component to variation in alcohol consumption in rhesus macaques would show for the first time that like humans, for nonhuman primates additive genetic influences are important. Moreover, their use as a model for alcohol-related disorders in humans would have even greater relevance and utility for designing experiments incorporating the expanding molecular genetics field, and allow researchers to investigate the interaction among the known environmental influences and various genotypes. Methods: In this study, we investigate factors contributing to variation in alcohol consumption of 156 rhesus macaques collected over 10 years when subjects were adolescent in age, belonging to a single extended pedigree, with each cohort receiving identical early rearing backgrounds and subsequent treatments. To measure alcohol consumption each animal was provided unfettered simultaneous access both to an aspartame-sweetened 8.4% (v/v) alcohol-water solution, the aspartame-sweetened vehicle, and to water for 1 hour each day during the early afternoon between 13:00 and 15:00 in their home cages for a period of 5 to 7 weeks. We use multiple regression to identify factors that significantly affect alcohol consumption among these animals and a maximum likelihood program (ASReml) that, controlling for the significant factors, estimates the genetic contribution to the variance in alcohol consumption. Results: Multiple regression analysis identified test cohort and rearing environment as contributing to 57 and 2%, respectively, of the total variance in alcohol consumption. Of the remaining 41% of the variance about half (19.8%) was attributable to additive genetic effects using a maximum likelihood program. Conclusion: This study demonstrates that, as in humans, there are additive genetic factors that contribute to variation in alcohol consumption in rhesus macaques, with other nongenetic factors accounting for substantial portions of the variance in alcohol consumption, Our findings show the presence of an additive genetic component and suggest the potential utility of the nonhuman primate as a molecular genetics tool for understanding alcohol abuse and alcoholism. [source] Heritability of the Blood Pressure Response to Acute Ethanol Exposure in Five Inbred Strains of MiceALCOHOLISM, Issue 10 2000Daniel C. Hatton Background: Chronic alcohol consumption is a major risk factor for hypertension. There is evidence in humans that the susceptibility to alcohol-related hypertension may vary based on genotype. As a first step in investigating the genetic basis for alcohol-related hypertension, the current study was designed to assess the heritability of the blood pressure response to acute ethanol exposure by using AKR/J (AK), C57BL/6J (B6), DBA/2J (D2), Balb/cJ (Balb), and A/J (A) mice. Methods: Mean arterial pressure (MAP) was recorded continuously for 24 hr in freely moving mice from an indwelling femoral catheter before we tested the effects of saline or ethanol (2 g/kg ip) on blood pressure. Results: Relative to saline, ethanol caused a pressor response that peaked within 10 min, followed by a decline in MAP. Strain A mice had a significantly greater pressor response to ethanol than other strains and did not show a decline in MAP below baseline. All other strains showed a progressive fall in blood pressure below baseline across the 60 min measurement interval. Heritability was estimated to be 0.62 for the pressor response and 0.64 for the maximal depressor response. Repeated doses of ethanol at 1 hr intervals in A and B6 mice (0,2,1.5,1.5,1.5 g/kg ip) resulted in a dose-dependent increase in MAP in A mice for the first three doses and a dose-dependent decrease in MAP in B6 mice that was independent of blood ethanol concentrations. Conclusion: The results indicate that there is a significant genetic component to the acute blood pressure response to ethanol. [source] Alcoholism Susceptibility Loci: Confirmation Studies in a Replicate Sample and Further MappingALCOHOLISM, Issue 7 2000Tatiana Foroud Background: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. Methods: Additional, genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. Results: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). Conclusions: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets. [source] Pleiotropic effects on subclasses of HDL, adiposity, and glucose metabolism in adult Alaskan EskimosAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2010M. Elizabeth Tejero The aim of this study was to analyze the heritability and the presence of pleiotropic effects on subfractions of high-density lipoproteins (HDLs) as measured by nuclear magnetic resonance (NMR), parameters for adiposity, and glucose metabolism in adult Alaskan Eskimos. The present family study included 1,214 adult Alaskan Eskimos (537 male/677 female). Body weight, height, circumferences, selected skinfolds, and blood pressure were measured in all participants. Blood samples were collected under fasting conditions for the isolation of plasma. Glucose, insulin, subclasses and size of lipoproteins, triglycerides, total, and HDL cholesterol and lipoprotein (a) were measured in plasma. HbA1c was measured in total blood. Univariate and bivariate quantitative genetic analyses were conducted between HDL subclasses and size and the anthropometric and biochemical measures using the variance decomposition approach. Variation in all the analyzed traits exhibits a significant genetic component. Heritabilities ranged between 0.18 ± 0.11 for LDL2 (intermediate) and 0.89 ± 0.07 for small HDL. No common genetic effects were found on the HDL subclasses (small, intermediate, and large). Small HDL particles were genetically correlated with LDL particles and HbA1c. Negative genetic correlations were observed between intermediate and large HDL subfractions, HDL size and measures of adiposity, and LDL and parameters for glucose metabolism (HbA1, insulin). These observations confirm the presence of possible pleiotropic effects on HDL, adiposity, and cardiovascular risk factors and provide novel insight on the relationship between HDL subclasses, adiposity, and glucose regulation. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] Loneliness in adolescence: gene × environment interactions involving the serotonin transporter geneTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 7 2010Eeske Van Roekel Background:, Loneliness is assumed to peak in early adolescence and to decrease throughout middle and late adolescence, but longitudinal confirmation of this tendency is lacking. Behavioral genetic studies with twin designs have found a significant genetic component for loneliness in children and adults, but no molecular genetic studies have been conducted to reveal the functional polymorphisms involved. Methods:, Associations among the serotonin transporter gene (5-HTTLPR), sex, parental support, and loneliness were examined in a longitudinal study spanning five annual waves (N = 306). Results:, Using latent growth curve modeling (LGCM), loneliness was found to be highest in early adolescence and slowly declined throughout adolescence. The 5-HTTLPR genotype was related to the development of loneliness, in that short allele carriers remained stable in loneliness over time, whereas adolescents with the long-long genotype decreased in loneliness. Interactions were found between maternal support and 5-HTTLPR genotype, showing that adolescents who perceived little support from their mothers and carried a short allele were at increased risk for developing loneliness. Conclusions:, Our study is the first to chart adolescent loneliness longitudinally and to examine the genetic underpinnings of loneliness. Our results contribute to a further understanding of the environmental and genetic basis of loneliness. Replication of our results is needed in both population-based and clinical samples. [source] Bronchomalacia occurring in monozygotic twins , further information about its inheritanceACTA PAEDIATRICA, Issue 9 2009Malcolm Brodlie We report left main-stem bronchomalacia occurring in monozygotic twins that became symptomatic during infancy. This phenomenon has not previously been reported to occur in twins. Little is known about the aetiology of primary bronchomalacia, but this occurrence suggests that there may be a significant genetic component in some cases. Conclusion:, Left main-stem bronchomalacia occurring in monozygotic twins suggests that there may be a significant genetic component in some cases and provides further information about the inheritance of this condition. [source] Common genetic influences underlie comorbidity of migraine and endometriosisGENETIC EPIDEMIOLOGY, Issue 2 2009Dale R. Nyholt Abstract We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12,2.21, P=0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (rG = 0.27, 95% CI: 0.06,0.47) and bivariate heritability (h2=0.17, 95% CI: 0.08,0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||