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Open Access Publications from the University of California

Scholarly Works (18 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 (2012)
                  Cover page: COMT Val158Met polymorphism interacts with stressful life events and parental warmth to influence decision makingCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2013)
                  DOPA decarboxylase (DDC) is involved in the synthesis of dopamine, norepinephrine and serotonin. It has been suggested that genes involved in the dopamine, norepinephrine, and cholinergic systems play an essential role in the efficiency of human attention networks. Attention refers to the cognitive process of obtaining and maintaining the alert state, orienting to sensory events, and regulating the conflicts of thoughts and behavior. The present study tested seven single nucleotide polymorphisms (SNPs) within the DDC gene for association with attention, which was assessed by the Attention Network Test to detect three networks of attention, including alerting, orienting, and executive attention, in a healthy Han Chinese sample (N=451). Association analysis for individual SNPs indicated that four of the seven SNPs (rs3887825, rs7786398, rs10499695, and rs6969081) were significantly associated with alerting attention. Haplotype-based association analysis revealed that alerting was associated with the haplotype G-A-T for SNPs rs7786398-rs10499695-rs6969081. These associations remained significant after correcting for multiple testing by max(T) permutation. No association was found for orienting and executive attention. This study provides the first evidence for the involvement of the DDC gene in alerting attention. A better understanding of the genetic basis of distinct attention networks would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped alerting attention as well as its related prevalent neuropsychiatric disorders.
                    Cover page: The DOPA decarboxylase (DDC) gene is associated with alerting attentionCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2013)
                    The genetic and neural basis of working memory (WM) has been extensively studied. Many dopamine (DA) related genes, including the NTSR1 gene (a DA modulator gene), have been reported to be associated with WM performance. The NTSR1 protein is predominantly expressed in the cerebral cortex and the hippocampus, the latter of which is closely involved in WM processing based on both lesion and fMRI studies. Thus far, however, no study has examined the joint effects of NTSR1 gene polymorphism and hippocampal morphology on WM performance. Participants of the current study were 330 healthy Chinese college students. WM performance was measured with a 2-back WM paradigm. Structural MRI data were acquired and then analyzed using an automated procedure with atlas-based FreeSurfer segmentation software (v 4.5.0) package. Linear regression analyses were conducted with a NTSR1 C/T polymorphism which was previously reported to be associated with WM (rs4334545), hippocampal volume, and their interaction as predictors of WM performance, with gender and intracranial volume (ICV) as covariates. Results showed a significant interaction between NTSR1 genotype and hippocampal volume (p<.05 for both the left and right hippocampi). Further analysis showed that the correlation between hippocampal volume and WM scores was significant for carriers of the NTSR1 T-allele (p<.05 for both hippocampi), but not for CC homozygotes. These results indicate that the association between hippocampal structure and WM performance was modulated by variation in the NTSR1 gene, and suggest that further studies of brain-behavior associations should take genetic background information into account.
                      Cover page: The NTSR1 gene modulates the association between hippocampal structure and working memory performanceCreative Commons 'BY' version 4.0 license
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