One psychosocial variable, human mate selection, has been studied extensively within the field of evolutionary psychology. A question of interest is how sexual/reproductive decision-making (i.e., dating, marrying, and childbearing) might be influenced by an individual’s perception of his/her genetic risk and other psychosocial variables. There is a paucity of empirical studies within the literature exploring this specific relationship. This partially mixed, sequential mixed methods study addresses how individual perception of genetic risk (PGR) influences or predicts sexual/reproductive intentions and decision-making. A systematic review of the literature was conducted by searching for English language, peer-reviewed, empirical studies in Cambridge Scientific Abstracts databases (N=26). Next, students from three Southwestern universities were recruited for focus groups and responded to 15 open-ended questions (N=86). Transcripts were audiotaped, transcribed verbatim and analyzed using holistic-content analysis. Based on the literature review and qualitative findings, a 138-item, web-based instrument was designed and tested at two Southwestern universities (N=2,576). Survey data were analyzed using non-parametric univariate analyses and multiple regression. Approximately 50 demographic, individual/familial psychosocial and genetic testing-related factors influenced the relationship between PGR and sexual/reproductive decision-making in reviewed studies. Individual psychosocial factors (e.g., intention, attitudes) represented 65.8% of all findings. Participants in the qualitative phase exhibited moderate health literacy when interpreting and discussing genetic risk information. A number of factors including age, gender, religion, individual/family values, and exposure to genetic concepts/technology appeared to influence sexual/reproductive decision-making. Demographic, Health Belief Model (HBM) and Theory of Planned Behavior (TPB) variables predicted the relationship between PGR and dating, marital, and childbearing intention in the quantitative phase. TPB variables were the strongest predictors of intention accounting for 33.1-38.7% of variance. Positive family norms were the single best predictor of dating and marital intention. Age was the best predictor of childbearing intention. Further research is needed to understand how young adults incorporate genetic risk perceptions into sexual/reproductive decision-making. Mixed methods and longitudinal study designs, and structural equation modeling are recommended for use in future studies. Study findings affirm a need for health educators to consider adopting genomic competencies; creating theory-based curricula/interventions; and forming partnerships with genetic specialists and local/regional health departments.

No description available.

The current study aimed to evaluate multiple longitudinal determinants of externalizing behavior problems in twins/triplets aged 7 to 12 years. Specifically, a prospective longitudinal design was utilized to assess relationships between age 5 sleep problems, age 5 temperament traits, and later externalizing problems. Additionally, heritability of sleep problems was assessed by utilizing the twin method, and genetic contributions of two specific genes – DRD4 and 5-HTTLPR – were evaluated. A total of 93 twins/triplets (40 boys and 53 girls) and their parents participated in the current study, and data were collected through self-report, parent-report, and molecular and behavioral genetic methods. Results suggest that sleep disturbances are significantly heritable, and that neither early sleep problems, temperament traits, nor specific genes significantly predicted follow-up externalizing problems. Post-hoc analyses assessing gene X environment interactions showed that externalizing problems were significantly predicted by the interaction between stressful life events and DRD4 risk, which is consistent with differential susceptibility models. This study has implications for future research as well as clinical practice, including for early screening, prevention, and intervention efforts aimed at decreasing childhood externalizing and sleep problems.

archives@tulane.edu / Background: Human Biological Aging (BA) estimates are developed by human to better capture the gradual increase in the vulnerability of the aging body than chronological age. Human sleep dimensions have been suggested to be associated with human health indicators including cardiometabolic function, cognitive function and mortality. The objective of this study was to examine indicators of BA and their predictive validity using Klemera and Doubal’s Method (KDM), and Physiological Dysregulation Method (PDM) for quantifying BA, as well as to explore if phenotypical and genetic associations between sleep variables and BA estimates exist, using the Bogalusa Heart Study (BHS) – a community-based, cohort study. Method: In order to estimate BA, nineteen biomarkers were selected. Training datasets were from NHANES. The target dataset included 1,034 BHS subjects assessed between 2013-2016. Training was done separately for male and female, black and white participants. KDM and Mahalanobis Distance (DM) based PDM methods were used. Cognitive and physical performance testing were used to examine predictive validity. The association between three sleep dimension variables and BA estimates were explored using 953 black and white BHS 2013-2016 subjects. Sleep duration in hours, chronotype scores and social jetlag in hours were the independent variables. BA estimates were the dependent variables. Genotyping information from the BHS 2013-2016 were included (n=646) for genetic association. Related SNPs on morning chronotype were used to compute a genetic risk score (GRS) for BHS participants. Association between chronotype GRS and chronotype phenotype were explored. Multivariate linear regression was used for all association analyses. Results: BA estimates were calculated using both the KDM and PDM methods. Linear regression showed that PDM BA estimates were associated with lower cognitive function physical performance tests. The effect sizes of all associations between PDM BA estimates and performance tests were of greater magnitude than between KDM estimates and performance tests. Short sleep duration and evening chronotype was associated with larger PDM BA estimates. Morning chronotype GRS was not associated with morning chronotype phenotype among BHS participants. Conclusion: PDM BA estimates are robust measures of biological aging in black and white men and women enrolled in the BHS. Insufficient sleep duration and evening chronotype may advance biological aging, regardless of gender, race and CA. We did not find association between morning chronotype GRS and morning chronotype phenotype. PDM BA estimates should be recommended for future aging studies using data from BHS participants. / 1 / Xunming Sun

While obesity is a world leading health problem, the most efficient treatment option for severely obese patients is Roux-Y gastric bypass (RYGB) surgery. However, there are large inter-individual differences in weight loss after RYGB surgery. The reasons for this are not yet elucidated and the role of genetics in weight loss-regulation is still not fully understood. The main aim for this thesis was to investigate the effects of common obesity-associated genetic variants and their effect on weight loss and food intake. We examined if the weight loss two years following RYGB surgery depends on the  FTO genotype, as well as pre-surgery vitamin D status. For FTO AA-carriers, the surgery resulted in a 3% per-allele increased excess BMI loss (EBMIL; P=0.02). When split by vitamin D baseline status, the EBMIL of vitamin D deficient patients carrying AA exceeded that of vitamin D deficient patients carrying TT by 14% (P=0.03). No such genotypic differences were found in patients without pre-surgery vitamin D deficiency. As the influence of individual single nucleotide polymorphisms may be small, we identified a novel method to combine SNPs into a genetic risk score (GRS). Using the random forest model, SNPs with high impact on weight loss after RYGB surgery were filtered out. An up to 11% lower EBMIL with higher risk score was estimated for the GRS model (p=0.026) composed of seven BMI-associated SNPs (closest genes: MC4R, TMEM160, PTBP2, NUDT3, TFAP2B, ZNF608 and MAP2K5). Pre-surgical hunger feelings were found to be associated with EBMIL and the SNP rs4846567. Before surgery, patients filled out the Three Factor Eating Questionnaire and were genotyped for known BMI and waist-hip ratio (WHR) associated SNPs. Patients with the lowest hunger scores had up to 32% greater EBMIL compared to the highest scoring patients (P=0.002). TT-allele carriers of rs4846567 showed a 58% lower hunger feelings. TT- carriers also showed a 51% decrease in disinhibition, but no significant impact on cognitive restraint was observed. Due to the association of eating behaviour and weight loss, acute effects on DNA methylation in response to a food intake intervention of a standardized meal were also investigated. After food intake, 1832 CpG sites were differentially methylated compared to the baseline after multiple testing correction. When adjusted for white blood cell fractions, 541 CpG sites remained. This may be interpreted as that the immune system is playing an active role in the response to food intake and highlights the dynamic nature of DNA-methylation. These findings will contribute to a better care for morbidly obese patients. Post-surgical treatment may be optimized so that patients with a less favourable genetic profile may receive additional support for weight loss and weight management. This may be considered as a step in the transition towards personalized medicine.

Thesis (Ph.D)--University of Tennessee Health Science Center, 2008. / Title from title page screen (viewed on January 6, 2009). Research advisor: Ann K. Cashion, Ph.D. Document formatted into pages (x, 102 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 81-88).

No description available.

Bipolar disorder is a heritable psychiatric disorder, and several of the genes associated with bipolar disorder and related psychotic disorders are involved in the development and maintenance of white matter in the brain. Patients with bipolar disorder have an increased incidence of white matter hyper-intensities, and quantitative brain imaging studies collectively indicate subtle decreases in white matter density and integrity in bipolar patients. This suggests that genetic vulnerability to psychosis may manifest itself as reduced white matter integrity, and that white matter integrity is an endophenotype of bipolar disorder. This thesis comprises a series of studies designed to test the role of white matter in genetic risk to bipolar disorder by analysis of diffusion tensor imaging (DTI) data in the Bipolar Family Study. Various established analysis methods for DTI, including whole-brain voxel-based statistics, tract-based spatial statistics (TBSS) and probabilistic neighbourhood tractography, were applied with fractional anisotropy (FA) as the outcome measure. Widespread but subtle white matter integrity reductions were found in unaffected relatives of patients with bipolar disorder, whilst more localised reductions were associated with cyclothymic temperament. Next, the relation of white matter to four of the most prominent psychosis candidate genes, NRG1, ErbB4, DISC1 and ZNF804A, was investigated. A core haplotype in NRG1, and three of the four key single nucleotide polymorphisms (SNPs) within it, showed an association with FA in the anterior thalamic radiations and the uncinate fasciculi. For the three SNPs considered in ErbB4, results were inconclusive, but this was consistent with the background literature. Most notable however, was a clear association of a non-synonymous DISC1 SNP, Ser704Cys, with FA extending over most of the white matter in the TBSS and voxel-based analyses. Finally, FA was not associated with a genome-wide supported risk SNP in ZNF804A, a finding which could not be attributed to a lack of statistical power, and which contradicts a strong, but previously untested hypothesis. Whilst the above results need corroboration from independent studies, other studies are needed to address the cellular and molecular basis of these findings. Overall, this work provides strong support for the role of white matter integrity in genetic vulnerability to bipolar disorder and the wider psychosis spectrum and encourages its future use as an endophenotype.

Abstract Sensorineural hearing impairment (SNHI) is a well-recognized manifestation of mitochondrial diseases and occurs either in a non-syndromic form or as a part of a syndrome. Mitochondrial deafness is bilateral, usually progressive and is inherited maternally. Approximately 70% of patients with the most common syndromes, Kearns-Sayre, MELAS or MERRF, have SNHI. Several mutations in mitochondrial DNA (mtDNA) have been found to cause non-syndromic SNHI, including 1555A>G, 7445T>C, 7472insC and 7511T>C. In order to estimate prevalences of pathogenic mtDNA mutations in population-based cohorts of patients with SNHI, we obtained samples from 133 patients with SNHI, reportedly representing 117 separate maternal lineages. We found five patients with the 3243A>G mutation and three with the 1555A>G mutation, whereas the other point mutations associated with SNHI were absent. The frequencies of the mutations in the cohort were thus 4.3 % for 3243A>G and 2.6 % for 1555A>G, suggesting a total frequency of 6.9 % for mtDNA mutations known to be associated with hearing impairment. We found a mutation 10044A>G, which has been reported as pathogenic, in our patients with SNHI, but we also found it among the controls. Our results show it to be a homoplasmic polymorphism associated with a fairly rare haplotype within mtDNA haplogroup H which has recently been confirmed as subcluster H4. These results highlight the difficulty in determining the pathogenicity of a mtDNA mutation when it is identified only in one family. Therefore, in addition to the previously published criteria, we suggest that a sufficient number of haplotype-specific controls should be screened before the pathogenic nature of a mtDNA mutation can be verified. We determined the complete mtDNA sequences for 121 Finns, and after complementing our recent data, for a total of 192 Finns, and were able to construct a phylogenetic network based on complete mtDNA sequences, the largest set of complete sequences available at that time. These mtDNAs provide a rich source of information for studies in population genetics and a potential tool for analysing new substitutions and genotypes that entail a risk of mitochondrial disease. We used the phylogenetic network to find new pathogenic mutations or risk genotypes for SNHI. The entire coding region sequences of mtDNA were determined in 32 patients with SNHI and compared with the network. The patients were found to harbour more rare polymorphisms and haplotypes than the controls and to show increased variation in their mtDNA sequences, suggesting mildly deleterious effects for these substitutions. Two of the new mutations were suggested as putatively pathogenic.

The serotonergic and cholinergic systems are jointly involved in regulating sleep but this balance is theorized to be disturbed in depressed individuals (Janowsky 1972, Jouvet 1972). One potential cause of disturbed neurotransmission is genetic predisposition. The G(-1019) allele of the 5-HT1A receptor predicts an increased risk for depression compared to the wild-type C(-1019) allele. The goal of this study was to use pharmacological probes in normal controls to model the serotonergic/cholinergic imbalance of depression and its associated abnormalities in sleep structure while controlling for 5-HT1A receptor genotype. Seventeen healthy female participants homozygous for either C (n=11) or G (n=6) alleles, age 18-27 years were tested on four non-consecutive nights. Participants were given galantamine (an anti-acetylcholinesterase), buspirone (a serotonergic agonist), both drugs together, or placebos before sleeping. Buspirone suppressed tonic REM: there was a significant increase in REM latency (p<0.001). Galantamine increased tonic REM sleep, leading to more time spent in stage REM (p<0.001) and shorter REM latency (p<0.01). Galantamine and buspirone given together tended to negate the effects of each other on REM sleep measures but disrupted sleep more than either drug alone, showing lower SE and N3% and increased awakenings, Wake% and N1% (p<0.019). There was no main effect of genotype nor was there a significant multivariate interaction between genotype and drug condition. These findings are partially consistent with the literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM, and increased sleep fragmentation. The C/G mutation in the 5-HT1A receptor does not appear to cause noticeable differences in the sleep patterns of healthy young females.