Faculty Bibliography

Epigenetic modifications of the membrane bound catechol-O-methyltransferase (MB-COMT) gene may affect the enzymatic degradation of dopamine, and consequently, human behavior. This study investigated the association between membrane bound catechol-O-methyltransferase DNA methylation (DNAm) differences in 92 monozygotic (MZ) twins with phenotypic manifestations of cognitive, behavioral, and personality indicators associated with reward-related behaviors and lack of control. We used pyrosequencing to determine DNAm of the regulatory region of membrane bound catechol-O-methyltransferase in saliva DNA. Results of intrapair differences in the percentage of membrane bound catechol-O-methyltransferase DNAm at each of five CpG sites show that there are associations between phenotypic indicators of lack of control and membrane bound catechol-O-methyltransferase DNAm differences on CpG1, CpG2 and CpG4, suggesting the common epigenetic patterns for personality traits, cognitive functions, and risk behaviors.

OBJECTIVE:The main goal of this study was to explore the latent structure and genetic basis of cognitive processes involved in the Wisconsin Card Sorting Task (WCST) within phenotypic, behavioral genetic, and molecular genetic research paradigms. METHOD/METHODS:The sample used in phenotypic and behavioral genetic analyses comprised 468 twins (154 monozygotic and 80 dizygotic twin pairs), while molecular genetic analyses were performed on 404 twins from the same sample. The zygosity of most twin pairs (96.8%) was determined via deoxyribonucleic acid (DNA) analysis of buccal swabs. Trained researchers administered the Wisconsin Card Sorting Test (WCST; Heaton et al., 1993) to the entire sample. RESULTS:Met- genotype. CONCLUSIONS:Met + genotype showed significant main effects on different WCST measures. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Two studies examined genetic and environmental influences on traits proposed by the revised Reinforcement Sensitivity Theory (rRST) of personality. Both quantitative and molecular behavioral genetic methods were applied considering the effects of COMT, DRD2, HTR1A and TPH2 single nucleotide polymorphisms (SNPs). Study one included 274 monozygotic and 154 dizygotic twins for the quantitative behavioral study; and in study two there were 431 twins for the molecular genetic study. The Reinforcement Sensitivity Questionnaire was used to assess basic personality traits defined by the rRST. Univariate biometric modeling suggested that genetic influences accounted for 34-44% of variance of Behavioral Approach System (BAS), Behavioral Inhibition System (BIS) and Fight-Fligh-Freeze System. Molecular genetic analyses proposed the significant main effect of COMT SNP on the BAS and TPH2 SNP on the BIS, and pointed out epistatic effects of COMT x DRD2 on BAS and HTR1A x TPH2 on Fight. Results demonstrated substantial heritability for all rRST constructs, as well as for differences in the molecular genetic basis of both approach-related and avoidance-related dimensions.

The main aim of this study was to explore the etiology of relations between general cognitive ability (g) and different hierarchical phenotypic levels of the Five Factor Model (FFM), including the General Factor of Personality (GFP), the Big Two, the five domains of the FFM, and their 30 facets. The second aim was to detect personality facets that contribute to the prediction of general intelligence. The sample consisted of 424 young adult twins (134 pairs of monozygotic twins) on whom the NEO-PI-R and Advanced Progressive Matrices were administered. The results did not support hierarchical solutions above the FFM. Thus, five-domain and facet level of personality were analyzed, showing that only Openness and Neuroticism had significant genetic or environmental correlations with intelligence. The several facets from all domains had significant associations, among which Ideas and Positive Emotions showed the highest positive correlations, while Order and Modesty showed the highest negative genetic correlations with intelligence. Furthermore, seven facets significantly predicted g factor (35%), with higher genetic (0.52) than environmental (0.13) correlations with intelligence. The results reveal the common genetic basis of narrow traits and intelligence, highlighting the importance of specific traits in the explanation of general cognitive abilities.

The aim of this study was to explore genetic and environmental contributions to laboratory-induced aggressive behavior. On a sample of 478 adult twins (316 monozygotic), the Competitive Reaction Time Task was used for aggression induction. The results showed that the initial, basic level of aggression could be explained by both shared (45%) and nonshared environmental factors (55%), while only nonshared environmental factors (100%) had a significant influence on changes in aggression as provocation increased. Genetic factors had no influence on laboratory-induced aggression. The results highlight the importance of environmental factors in shaping situation-specific aggressive responses to provocation.

The first aim of this study was to explore the aetiology of phenotypic relationships between different measures of executive functions. The second objective was to examine sources of the covariation between different measures of executive functions and the measure of general cognitive ability. The study sample consisted of 468 twins (154 pairs of monozygotic twins and 80 pairs of dizygotic twins) of the same and different gender who grew up together. Executive functions were evaluated by the Wisconsin Card Sorting Test, the Trail Making Test "“ form B, and verbal fluency tests. Raven's Advanced Progressive Matrices were used as a measure of general cognitive ability. The study results suggest a primarily genetic origin of the mutual covariation of different executive measures and their covariation with the general cognitive ability construct. While the shared genetic variance primarily lies in the bases of similarity/unity of the used cognitive measures, their particularity/difference is determined by a specific unshared environment. The obtained result on the presence of a single general genetic factor, which can be singled out in the case of different executive measures, at least partially speaks in favor of the thesis about the unity of various executive measures and the existence of a common basic ability. Together with the specific unshared environment, the specific genetic influence speaks in favor of a difference between each of the individual measures.

This study examines cultural differences in genetic and environmental influences on Five-Factor Model (FFM) across Croatian, German and Serbian cultures. Participants were 1021 monozygotic and 722 dizygotic twin pairs and NEO Five-Factor Inventory"“ NEO-FFI is used to assess FFM personality traits. Results show a similar pattern of genetic and environmental contribution to the variance of all FFM dimensions, indicating that culture has no significant effect on the genetic and environmental variance of personality traits. The best fitted common factor - common AE pathway models show that FFM dimensions are accounted for by the common latent factor. Although FFM dimensions clearly share some common sources of variance, the effects of specific genetic and environmental factors are more pronounced than common ones. Different patterns of genetic and environmental correlations across three samples may reflect the way that the synergy of personality traits responds to the specificities of a particular culture, as well as possible subtle differences in item translation, testing conditions, and measurement error.

Identifying human remains is one of the many responsibilities of forensic scientists. An eye- and skin-color predictor translates genotypic information into phenotypic description. Eight single nucleotide polymorphisms (SNPs) are utilized for this predictor, five for eye, and six for skin coloration. Here, we describe the development and validation of an 8-SNP multiplex assay that consists of a multiplex PCR, followed by a multiplexed single-base primer extension reaction generating fluorescently labeled oligonucleotides of distinct length that are detected by multicolor capillary electrophoresis. Validation of this assay included tests for reproducibility, reliability, sensitivity, species specificity, its performance on degraded DNA, and on forensic samples. It can be concluded that the 8-SNP multiplex assay is robust and can be used on challenging samples, including bones, to reliably determine the genotypes to predict eye and skin color of individuals. This information can assist in the identification of human remains and missing persons.

Sequencing mitochondrial DNA hypervariable regions I and II (HVI and HVII) is useful in forensic missing person and unidentified remains cases. Improvements in ease and sensitivity of testing will yield results from more samples in a timely fashion. Routinely, amplification of HVI and HVII is followed by Sanger sequencing using the BigDye(R) Terminator v3.1 Cycle Sequencing kit (Applied Biosystems) using 4 muL of ready reaction mix (RRM). Each sequencing reaction is then purified through column filtration before capillary electrophoresis. Using lower amounts of RRM (2 muL or 1 muL) and purification using BigDye(R) XTerminator (Applied Biosystems) instead of columns showed no loss of sequence length and increased the quality and the sensitivity of testing, allowing HVI and HVII typing from mitochondrial genome equivalent to 125 fg of nuclear DNA, or 100 pg of HVI/HVII amplicons. Using this methodology, testing can be completed in 1 day, and the cost of testing is reduced.

Sudden unexplained deaths (SUD) in apparently healthy individuals, for which the causes of deaths remained undetermined after comprehensive forensic investigations and autopsy, present vexing challenges to medical examiners and coroners. Cardiac channelopathies, a group of inheritable diseases that primarily affect heart rhythm by altering the cardiac conduction system, have been known as one of the likely causes of SUD. Adhering to the recommendations of including molecular diagnostics of cardiac channelopathies in SUD investigation, the Molecular Genetics Laboratory of the New York City (NYC) Office of Chief Medical Examiner (OCME) has been routinely testing for six major channelopathy genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RyR2) since 2008. Presented here are the results of cardiac channelopathy testing in 274 well-characterized autopsy negative SUD cases, all with thorough medicolegal death investigation including complete autopsy by NYC OCME between 2008 and 2012. The cohort consisted of 141 infants (92.9% younger than six-month old) and 133 non-infants (78.2% were between 19 and 58 years old). Among the ethnically diverse cohort, African American infants had the highest risks of SUD, and African American non-infants died at significantly younger age (23.7 years old, mean age-at-death) than those of other ethnicities (30.3 years old, mean age-at-death). A total of 22 previously classified cardiac channelopathy-associated variants and 24 novel putative channelopathy-associated variants were detected among the infants (13.5%) and non-infants (19.5%). Most channelopathy-associated variants involved the SCN5A gene (68.4% in infants, 50% in non-infants). We believe this is the first study assessing the role of cardiac channelopathy genes in a large and demographically diverse SUD population drawn from a single urban medical examiner's office in the United States. Our study supports that molecular testing for cardiac channelopathy is a valuable tool in SUD investigations and provides helpful information to medical examiners/coroners seeking cause of death in SUD as well as potentially life-saving information to surviving family members.