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Open Access Publications from the University of California

Scholarly Works (26 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2019)

This study aims to shed light on genetic variation among Armenians, an understudied population. Given the increasing uptake of genetic testing in various settings, the lack of published research poses a significant barrier to providing precise and thorough genetic counseling to Armenian individuals. By analyzing exome sequence from 44 Armenian individuals for 176 genes related to conditions commonly tested for in expanded carrier screening, expanded carrier screening positive rates (ECS-PRs) were calculated for individuals in this study. Fifty-two percent of individuals in this cohort were found to be a carrier of a pathogenic variant for at least one recessive condition. A total of seven out of 44 individuals were found to be carriers for familial Mediterranean fever; however, when FMF was excluded from ECS-PR calculation, the percentage of individuals who were found to be a carrier of a pathogenic variant for at least one recessive condition only decreased by 4%, yielding an ECS-PR of 48%. There were also two individuals with the same CFTR pathogenic variant, four individuals with four distinct PAH variants, and two individuals with two distinct PMM2 variants. This study provides data to a recommendation of expanded carrier screening in Armenian individuals as compared to targeted testing for FMF only. Results of this study will improve genetic counseling provided to Armenian individuals, particularly in prenatal and pre-conceptional settings, and promote diversity and equity in the field of genetics to improve the overall quality of services for providers and patients alike.

    Cover page: An Evaluation of Variants Associated with 176 Conditions Identified through Exome Sequencing in an Armenian Sample
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2013)
    Previous research reported that serotonin receptor 2A gene (HTR2A) polymorphisms were associated with memory. However, it is unknown whether these genetic variants were associated with both true and false memories. The current study of 336 Han Chinese subjects tested 30 single nucleotide polymorphisms (SNPs) within the HTR2A gene for potential associations with true and false memories. False memories were assessed using the Deese-Roediger-McDermott (DRM) paradigm, in which people falsely remember semantically related (but unpresented) words. We found that 11 SNPs within the HTR2A gene were associated with true memory (p=0.000076-0.043). The associations between true memory and seven adjacent SNPs (i.e., rs1923888, rs1745837, rs9567739, rs3742279, rs655888, rs655854, and rs2296972) were still significant after multiple testing corrections. Haplotype-based association analysis revealed that, true memory was positively associated with haplotype A-C-C-G-C-T-A for these seven adjacent SNPs (p=0.000075), which was still significant after multiple testing correction. Only one SNP rs655854 was associated with false memory (p=0.023), and it was not significant after multiple testing correction. This study replicates, in an Asian population, that genetic variation in HTR2A is associated with episodic memory, and also suggests that this association is restricted to true memory.
      Cover page: True but not false memories are associated with the HTR2A gene
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2012)
      Previous research reported that a rare serotonin receptor 2B gene (HTR2B) stop codon mutation predisposes subjects to severe impulsivity and novelty seeking. In this study, we expanded this previous work by testing six single nucleotide polymorphisms (SNPs) within the HTR2B gene for potential associations with the behavioral inhibition system (BIS) and the three components of the behavioral approach systems (BAS: fun seeking, drive, and reward responsiveness) in a Han Chinese sample (N= 478). Association analysis for individual SNPs indicated that four of the six SNPs (i.e., rs6437000, rs10194776, rs16827801, and rs1549339) were significantly associated with BAS fun seeking (p= 0003-0022). Haplotype-based association analysis revealed that fun seeking was positively associated with haplotype A-A-G-A for SNPs rs6437000- rs10194776- rs16827801- rs1549339 (p= 0002), which survived Bonferroni correction. Except for the association between BAS reward responsiveness and rs16827801 (p= 005), no other association was found for BAS drive, BAS reward responsiveness, or BIS. This study provides the first evidence for the involvement of the HTR2B gene in BAS fun seeking. A better understanding of the genetic basis of the BIS and BAS would allow us to develop more effective diagnosis, treatment, and prevention of impulsive behavioral problems. © 2012 Elsevier Ltd.
        Cover page: Association between the HTR2B gene and the personality trait of fun seekingCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2013)
          Cover page: Genotypes over-represented among college students are linked to better cognitive abilities and socioemotional adjustmentCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2011)
          Background

          Recent molecular genetics studies showed significant associations between dopamine-related genes (including genes for dopamine receptors, transporters, and degradation) and working memory, but little is known about the role of genes for dopamine modulation, such as those related to neurotensin (NT), in working memory. A recent animal study has suggested that NT antagonist administration impaired working memory in a learning task. The current study examined associations between NT genes and working memory among humans.

          Methods

          Four hundred and sixty healthy undergraduate students were assessed with a 2-back working memory paradigm. 5 SNPs in the NTSR1 gene were genotyped. 5 ANOVA tests were conducted to examine whether and how working memory differed by NTSR1 genotype, with each SNP variant as the independent variable and the average accuracy on the working memory task as the dependent variable.

          Results

          ANOVA results suggested that two SNPs in the NTSR1 gene (rs4334545 and rs6090453) were significantly associated with working memory. These results survived corrections for multiple comparisons.

          Conclusions

          Our results demonstrated that NTSR1 SNP polymorphisms were significantly associated with variance in working memory performance among healthy adults. This result extended previous rodent studies showing that the NT deficiency impairs the working memory function. Future research should replicate our findings and extend to an examination of other dopamine modulators.

            Cover page: Neurotensin Receptor 1 Gene (NTSR1) Polymorphism Is Associated with Working MemoryCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2016)
            Cooperativeness is an essential behavioral trait evolved to facilitate group living. Social and cognitive mechanisms involved in cooperation (e.g., motivation, reward encoding, action evaluation, and executive functions) are sub-served by the striatal-projected circuits, whose physical existence has been confirmed by animal studies, human postmortem studies, and in vivo human brain studies. The current study investigated the associations between Cooperativeness and fiber connectivities from the striatum to nine subcortical and cortical regions, including the amygdala, hippocampus, medial orbitofrontal cortex, lateral orbitofrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate cortex/retrosplenial cortex, dorsal cingulate cortex, and rostral cingulate cortex. Results showed that Cooperativeness was negatively correlated with fiber connectivity for the cognitive control system (from the dorsal caudate to the rostral cingulate cortex and ventrolateral prefrontal cortex), but not with fiber connectivity for the social cognitive system (e.g., connectivity with the medial prefrontal cortex and amygdala). These results partially supported Declerck et al.'s (2013) cognitive neural model of the role of cognitive control and social cognition in cooperation.
              Cover page: Striatum-Centered Fiber Connectivity Is Associated with the Personality Trait of CooperativenessCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2015)
              The amygdala plays a critical role in emotion processing and psychiatric disorders associated with emotion dysfunction. Accumulating evidence suggests that amygdala structure is modulated by serotonin-related genes. However, there is a gap between the small contributions of single loci (less than 1%) and the reported 63-65% heritability of amygdala structure. To understand the "missing heritability," we systematically explored the contribution of serotonin genes on amygdala structure at the gene set level. The present study of 417 healthy Chinese volunteers examined 129 representative polymorphisms in genes from multiple biological mechanisms in the regulation of serotonin neurotransmission. A system-level approach using multiple regression analyses identified that nine SNPs collectively accounted for approximately 8% of the variance in amygdala volume. Permutation analyses showed that the probability of obtaining these findings by chance was low (p = 0.043, permuted for 1000 times). Findings showed that serotonin genes contribute moderately to individual differences in amygdala volume in a healthy Chinese sample. These results indicate that the system-level approach can help us to understand the genetic basis of a complex trait such as amygdala structure.
                Cover page: Genetic variations in the serotonergic system contribute to amygdala volume in humans
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2011)
                Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies.
                  Cover page: Contributions of Dopamine-Related Genes and Environmental Factors to Highly Sensitive Personality: A Multi-Step Neuronal System-Level ApproachCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2011)
                  Previous research has shown inconsistent findings regarding the relations between the functional Val158Met polymorphisms of the catechol-O-methyltransferase (COMT) gene and individual differences in personality traits. This study attempts to overcome some of the weaknesses of previous research, namely, small sample sizes, clinical samples, ethnic stratification, wide age ranges, neglecting sex differences, and single measures of personality traits. A large sample (n = 556, 250 male, 306 female) of healthy Chinese college students (mean age = 20.5 ± 1 years) was given a battery of personality scales, including the temperament and character inventory-revised, the behavioral inhibition system and behavioral approach system scale, the Beck depression inventory, and the Beck anxiety inventory. Factor analysis of the affect-related personality traits revealed two factors that corresponded to positive (PEM) and negative emotionality (NEM). We found a consistent COMT-by-sex interaction effect on affect-related personality traits. Compared with males with Met/Met alleles, males with Val/Val alleles showed significantly higher scores on NEM, but lower scores on PEM. Females, however, showed an opposite but nonsignificant pattern. Our results supported the role of the COMT gene in personality traits for males and contributed to the growing literature on sex differences in gene-behavior connections.
                    Cover page: Sex Modulates the Associations Between the COMT Gene and Personality TraitsCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2000)
                    Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993-998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121-124: Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998;3:38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.
                      Cover page: Dopamine genes and ADHDCreative Commons 'BY' version 4.0 license
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