Attention-deficit/hyperactivity disorder and dopamine receptor D4 (DRD4) exon 3 variable number of tandem repeats (VNTR) 2-repeat allele.

To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64-1.3). The p-value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12-0.92) and p = 0.03. Because our study used TDT analysis, we meta-analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80-1.2) and p = 0.8. To examine the association of 2R with inattentive ADHD, we meta-analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57-1.1) and p = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation.

The Choline Acetyltransferase (CHAT) Gene is Associated with Parahippocampal and Hippocampal Structure and Short-term Memory Span.

The CHAT gene encodes choline acetyltransferase, which is an enzyme responsible for the biosynthesis of the neurotransmitter acetylcholine in the brain. This study collected structural MRI, genetic, and behavioral data from 324 healthy Chinese adults, and examined the associations between CHAT genetic variants, parahippocampal and hippocampal structure, and short-term memory span. After controlling for intracranial volume, sex, and age, CHAT SNP rs12246528 had the strongest association with parahippocampal structure, with the A allele being linked to smaller volume, surface area, and thickness. SNP rs1917814 had the strongest association with hippocampal volume, with the T allele being linked to larger hippocampal volume. After controlling for sex and age, CHAT rs3729496 had the strongest association with memory span, with the T allele being associated with a greater memory span. Finally, the left parahippocampal gyrus surface area was positively associated with memory span. This study provides the first evidence for the involvement of the CHAT gene in parahippocampal and hippocampal structures and memory span in healthy Chinese adults.

Family-based association study of DRD4 gene in methylphenidate-responded Attention Deficit/Hyperactivity Disorder.

The 48-basepair (48-bp) variable number tandem repeat (VNTR) polymorphism in exon 3 of the dopamine receptor D4 gene (DRD4) is implicated in the etiology of attention-deficit/ hyperactivity disorder (ADHD). In particular, ADHD in European-ancestry population is associated with an increased prevalence of the 7-repeat (7R) allele of the exon 3 VNTR. However, it is intriguing to note that the 7R allele has been found to be of very low prevalence in the Chinese general population. In a previous case-control study, our research team had found that the 7R allele was similarly absent in Chinese ADHD children in Hong Kong. Instead, there was an increased prevalence of the 2R allele in Chinese ADHD children. Interestingly, in Asian samples, the 2R allele had been found to be an evolutionary derivative of the 7R allele with equivalent biochemical functionality. So, the finding of an association between ADHD and 2R allele in Chinese population does not exactly contradict the original 7R allele finding in European-ancestry population. However, given the potential pitfall of population stratification in the previous case-control design, this current study tested the 2R allele and ADHD association using a methodologically more rigorous family-based approach on 33 Chinese ADHD probands who had favorable clinical responses to stimulant medication (methylphenidate). Haplotype Relative Risk (HRR) analysis and Transmission Disequilibrium Test (TDT) both showed a significant preferential transmission of the 2R allele from the biological parents to ADHD probands (pone-tailed = 0.038, OR = 2.04; pone-tailed = 0.048, OR = 2.29, respectively). A second hypothesis speculates that it is the deviation, including 7R and 2R alleles, from the conserved ancestral 4R allele which confers risk to ADHD. Thus, a preferential transmission of non-4R alleles, against the 4R allele, from biological parents to their ADHD probands is predicted. Both HRR analysis and TDT confirmed such prediction (pone-tailed = 0.029, OR = 2.07; pone-tailed = 0.032, OR = 2.43, respectively). This study re-confirmed the original finding of a previous study that in Chinese population, the 2R allele of the DRD4 exon 3 VNTR was related to ADHD. This endorses the general thesis that DRD4 exon 3 VNTR polymorphism is related to ADHD, despite that the exact length or number of repeats of the associated alleles varies across ethnicity. This in turn supports the dopamine dysregulation theory of ADHD.

Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task.

The CNTNAP2 (contactin-associated protein-like 2) gene, highly expressed in the human prefrontal cortex, has been linked with autism and language impairment. Potential relationships between CNTNAP2, dorsolateral prefrontal cortex (DLPFC), and cognition have been suggested by previous clinical studies, but have not been directly examined in the same study. The current study collected structural MRI, genetic, and behavioral data in 317 healthy Chinese adults, and examined associations between CNTNAP2 variants, DLPFC, and cognitive performance (measured by the Stroop task). After controlling for intracranial volume, sex, and age, the CNTNAP2 genetic polymorphism at SNP rs7809486 had the strongest association with bilateral DLPFC volume (p=0.00015 and 0.00014 for left and right DLPFC volumes, respectively), with GG homozygotes having greater bilateral DLPFC volumes and surface areas than the other genotypes. Furthermore, TT homozygotes of CNTNAP2 rs4726946 (a nearby SNP that had moderate linkage disequilibrium with rs7809486) had greater left DLPFC volume and surface area, and better cognitive performance than the other genotypes. Subjects with greater left DLPFC surface area had better cognitive performance. Importantly, the left DLPFC surface area mediated the association between the CNTNAP2 rs4726946 genotype and cognitive performance. This study provides the first evidence for associations among the CNTNAP2 gene, left DLPFC structure, and cognitive control.

Striatum-Centered Fiber Connectivity Is Associated with the Personality Trait of Cooperativeness.

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.

Gender Interacts with Opioid Receptor Polymorphism A118G and Serotonin Receptor Polymorphism -1438 A/G on Speed-Dating Success.

We examined an understudied but potentially important source of romantic attraction-genetics-using a speed-dating paradigm. The mu opioid receptor (OPRM1) polymorphism A118G (rs1799971) and the serotonin receptor (HTR2A) polymorphism -1438 A/G (rs6311) were studied because they have been implicated in social affiliation. Guided by the social role theory of mate selection and prior genetic evidence, we examined these polymorphisms' gender-specific associations with speed-dating success (i.e., date offers, mate desirability). A total of 262 single Asian Americans went on speed-dates with members of the opposite gender and completed interaction questionnaires about their partners. Consistent with our prediction, significant gender-by-genotype interactions were found for speed-dating success. Specifically, the minor variant of A118G (G-allele), which has been linked to submissiveness/social sensitivity, predicted greater speed-dating success for women, whereas the minor variant of -1438 A/G (G-allele), which has been linked to leadership/social dominance, predicted greater speed-dating success for men. For both polymorphisms, reverse "dampening" effects of minor variants were found for opposite-gender counterparts. These results support previous research on the importance of the opioid and serotonergic systems in social affiliation, indicating that their influence extends to dating success, with opposite, yet gender-norm consistent, effects for men and women.

Genetic variations in the serotonergic system contribute to amygdala volume in humans.

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.

Increased brain activity to unpleasant stimuli in individuals with the 7R allele of the DRD4 gene.

The aim of the study was to examine functional brain activity in response to unpleasant images in individuals with the 7-repeat (7R) allele compared to individuals with the 4-repeat (4R) allele of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3). Based on the response ready hypothesis, individuals with the DRD4-4R/7R genotype were expected to show greater functional brain activity in response to unpleasant compared to neutral stimuli in specific regions of the frontal, temporal, parietal and limbic lobes, which form the networks involved in attentional, emotional, and preparatory responses. Functional Magnetic Resonance Imaging activity was studied in 26 young adults (13 with the DRD4-4R/7R genotype and 13 with the DRD4-4R/4R genotype). Participants were asked to look at and subjectively rate unpleasant and neutral images. Results showed increased brain activity in response to unpleasant images compared to neutral images in the right temporal lobe in participants with the DRD4-4R/7R genotype versus participants with the DRD4-4R/4R genotype. The increase in right temporal lobe activity in individuals with DRD4-4R/7R suggests greater involvement in processing negative emotional stimuli. Intriguingly, no differences were found between the two genotypes in the subjective ratings of the images. The findings corroborate the response ready hypothesis, which suggests that individuals with the 7R allele are more responsive to negative emotional stimuli compared to individuals with the 4R allele of the DRD4 gene.

The GABRB1 gene is associated with thalamus volume and modulates the association between thalamus volume and intelligence.

The GABRB1 gene encodes the beta 1 subunit of the gamma-aminobutyric acid A receptor (GABA A receptor), which is responsible for mediating inhibitory neurotransmission in the thalamus. Potential relationships between the GABRB1 gene, thalamus volume, and intelligence have been suggested by previous clinical studies, but have not been directly examined among nonclinical samples. The current study collected structural MRI, genetic, and behavioral data from 316 healthy Chinese adults (including 187 females and 129 males), and examined associations between GABRB1 variants, thalamus volume, and intelligence (measured by the Wechsler Adult Intelligence Scale Revised). After controlling for intracranial volume, sex, and age, GABRB1 genetic polymorphism at the SNP rs7435958 had the strongest association with thalamus volume (p = 0.002 and 0.00008 for left and right thalamus volumes, respectively), with GG homozygotes having smaller bilateral thalamus volumes than the other genotypes. Furthermore, there were positive correlations between bilateral thalamus volumes and intelligence, especially for GABRB1 rs7435958 GG female homozygotes (r's = 0.31 and 0.29, p < 0.01, for the correlations of intelligence with left and right thalamus volumes, respectively). This study provides the first evidence for the involvement of the GABRB1 gene in the thalamus structure and their interactive effects on intelligence. Future studies of the thalamus-intelligence associations should consider genetic factors as potential moderators.

Preadoption adversity, MAOA, and behavioral adjustment in internationally adopted Chinese girls.

OBJECTIVES: We studied postinstitutionalized adopted Chinese girls to determine whether those with different variants of the MAOA gene promoter region (MAOA-VNTR) differed in their internalizing and externalizing behavior problems and whether the MAOA genotype moderated the relation between preadoption adversity and current behavior problems. METHODS: MAOA genotyping was obtained for 94 girls (mean age: 9.2 years) and the number of 4-repeat (4R) alleles was determined (zero, one, or two). The adoptive mothers rated several indicators of preadoption adversity shortly after adoption (mean age at adoption 15.8 months) and completed the Child Behavior Checklist when the children were 8.1 years on average. RESULTS: No main effects were found for preadoption adversity. However, the MAOA genotype had a nominally significant effect (P<0.05) on internalizing problems. Regression analyses controlling for age, household income, authoritarian parenting, and family problems showed that among children with no physical signs of preadoption adversity, those carrying a greater number of 4R alleles scored significantly lower (P<0.01) on internalizing problems than those with fewer 4R alleles. Differences in internalizing scores related to the MAOA genotype were not observed for children who showed one or more physical signs of adversity at the time of adoption. A similar pattern was found for externalizing problems, although the results did not reach conventional levels of significance. CONCLUSION: Our results suggest that higher MAOA activity may be protective with respect to internalizing problems in internationally adopted Chinese girls, but that this protective effect decreases at higher levels of preadoption adversity. A similar pattern may exist for externalizing problems.

Fiber connectivity between the striatum and cortical and subcortical regions is associated with temperaments in Chinese males.

The seven-factor biopsychosocial model of personality distinguished four biologically based temperaments and three psychosocially based characters. Previous studies have suggested that the four temperaments-novelty seeking (NS), reward dependence (RD), harm avoidance (HA), and persistence (P)-have their respective neurobiological correlates, especially in the striatum-connected subcortical and cortical networks. However, few studies have investigated their neurobiological basis in the form of fiber connectivity between brain regions. This study correlated temperaments with fiber connectivity between the striatum and subcortical and cortical hub regions in a sample of 50 Chinese adult males. Generally consistent with our hypotheses, results showed that: (1) NS was positively correlated with fiber connectivity from the medial and lateral orbitofrontal cortex (mOFC, lOFC) and amygdala to the striatum; (2) RD was positively correlated with fiber connectivity from the mOFC, posterior cingulate cortex/retrosplenial cortex (PCC), hippocampus, and amygdala to the striatum; (3) HA was positively linked to fiber connectivity from the dorsolateral prefrontal cortex (dlPFC) and PCC to the striatum; and (4) P was positively linked to fiber connectivity from the mOFC to the striatum. These results extended the research on the neurobiological basis of temperaments by identifying their anatomical fiber connectivity correlates within the subcortical-cortical neural networks.

The SEMA5A gene is associated with hippocampal volume, and their interaction is associated with performance on Raven's Progressive Matrices.

The Allen Brain Atlas shows that the semaphorin 5A (SEMA5A) gene, which encodes an important protein for neurogenesis and neuronal apoptosis, is predominantly expressed in the human hippocampus. Structural and functional neuroimaging studies have further shown that the hippocampus plays an important role in the performance on Raven's Progressive Matrices (RPM), a measure of reasoning ability and general fluid intelligence. Thus far, however, no study has examined the relationships between the SEMA5A gene polymorphism, hippocampal volume, and RPM performance. The current study collected both structural MRI, genetic, and behavioral data in 329 healthy Chinese adults, and examined associations between SEMA5A variants, hippocampal volume, and performance on RAPM (the advanced form of RPM). After controlling for intracranial volume (ICV), sex, and age, SEMA5A genetic polymorphism at the SNP rs42352 had the strongest association with hippocampal volume (p=0.00000552 and 0.000103 for right and left hippocampal volumes, respectively), with TT homozygotes having higher hippocampal volume than the other genotypes. Furthermore, there was a high correlation between right hippocampal volume and RAPM performance (r=0.42, p=0.0000509) for SEMA5A rs42352 TT homozygotes. This study provides the first evidence for the involvement of the SEMA5A gene in hippocampal structure and their interaction on RAPM performance. Future studies of the hippocampus-RPM associations should consider genetic factors as potential moderators.

True but not false memories are associated with the HTR2A gene.

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.

DRD4 genotype predicts longevity in mouse and human.

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90-109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7-45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10(-9)), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.

The DOPA decarboxylase (DDC) gene is associated with alerting attention.

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.

The NTSR1 gene modulates the association between hippocampal structure and working memory performance.

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.

Gene-environment interaction in problematic substance use: interaction between DRD4 and insecure attachments.

To investigate the combined effect of an exon III variable number tandem repeat in the dopamine receptor gene (DRD4) and insecure attachment style on risk for tobacco, cannabis and alcohol use problems in young adulthood. It was hypothesized that (1) individuals with 5, 6, 7 or 8 repeats (labelled 7R+) would be at increased risk for problematic drug use, and (2) risk for drug use would be further increased in individuals with 7R+ repeats who also have a history of insecure parent-child attachment relations. Data were drawn from the Victorian Adolescent Health Cohort Study, an eight-wave longitudinal study of adolescent and young adult development. DRD4 genotypes were available for 839 participants. Risk attributable to the combined effects of 7R+ genotype and insecure attachments was evaluated within a sufficient causes framework under the assumptions of additive interaction using a two-by-four table format with a common reference group. 7R+ alleles were associated with higher tobacco, cannabis and alcohol use (binging). Insecure attachments were associated with higher tobacco and cannabis use but lower alcohol use. For tobacco, there was evidence of interaction for anxious but not avoidant attachments. For cannabis, there was evidence of interaction for both anxious and avoidant attachments, although the interaction for anxious attachments was more substantial. There is no evidence of interaction for binge drinking. Results are consistent with a generic reward deficit hypothesis of drug addiction for which the 7R+ disposition may play a role. Interaction between 7R+ alleles and attachment insecurity may intensify risk for problematic tobacco and cannabis use.

COMT Val158Met polymorphism interacts with stressful life events and parental warmth to influence decision making.

Both genetic and environmental factors have been shown to influence decision making, but their relative contributions and interactions are not well understood. The present study aimed to reveal possible gene-environment interactions on decision making in a large healthy sample. Specifically, we examined how the frequently studied COMT Val(158)Met polymorphism interacted with an environmental risk factor (i.e., stressful life events) and a protective factor (i.e., parental warmth) to influence affective decision making as measured by the Iowa Gambling Task. We found that stressful life events acted as a risk factor for poor IGT performance (i.e., high reward sensitivity) among Met carriers, whereas parental warmth acted as a protective factor for good IGT performance (i.e., higher IGT score) among Val/Val homozygotes. These results shed some new light on gene-environment interactions in decision making, which could potentially help us understand the underlying etiology of several psychiatric disorders associated with decision making impairment.

Sex determines which section of the SLC6A4 gene is linked to obsessive-compulsive symptoms in normal Chinese college students.

Previous case-control and family-based association studies have implicated the SLC6A4 gene in obsessive-compulsive disorder (OCD). Little research, however, has examined this gene's role in obsessive-compulsive symptoms (OCS) in community samples. The present study genotyped seven tag SNPs and two common functional tandem repeat polymorphisms (5-HTTLPR and STin2), which together cover the whole SLC6A4 gene, and investigated their associations with OCS in normal Chinese college students (N = 572). The results revealed a significant gender main effect and gender-specific genetic effects of the SLC6A4 gene on OCS. Males scored significantly higher on total OCS and its three dimensions than did females (ps < .01). The 5-HTTLPR in the promoter region showed a female-specific genetic effect, with the l/l and l/s genotypes linked to higher OCS scores than the s/s genotype (ps < .05). In contrast, a conserved haplotype polymorphism (rs1042173| rs4325622| rs3794808| rs140701| rs4583306| rs2020942) covering from intron 3 to the 3' UTR of the SLC6A4 gene showed male-specific genetic effects, with the CGAAGG/CGAAGG genotype associated with lower OCS scores than the other genotypes (ps < .05). These effects remained significant after controlling for OCS-related factors including participants' depressive and anxiety symptoms as well as stressful life events, and correction for multiple tests. These results are discussed in terms of their implications for our understanding of the sex-specific role of the different sections of the SLC6A4 gene in OCD.

Genetic variations in the dopamine system and facial expression recognition in healthy chinese college students.

OBJECTIVE: This study investigated the relation between genetic variations in the dopamine system and facial expression recognition. METHODS: A sample of Chinese college students (n = 478) was given a facial expression recognition task. Subjects were genotyped for 98 loci [96 single-nucleotide polymorphisms (SNPs) and 2 variable number tandem repeats] in 16 genes involved in the dopamine neurotransmitter system, including its 4 subsystems: synthesis (TH, DDC, and DBH), degradation/transport (COMT,MAOA,MAOB, and SLC6A3), receptors (DRD1,DRD2,DRD3,DRD4, and DRD5), and modulation (NTS,NTSR1,NTSR2, and NLN). To quantify the total contributions of the dopamine system to emotion recognition, we used a series of multiple regression models. Permutation analyses were performed to assess the posterior probabilities of obtaining such results. RESULTS: Among the 78 loci that were included in the final analyses (after excluding 12 SNPs that were in high linkage disequilibrium and 8 that were not in Hardy-Weinberg equilibrium), 1 (for fear), 3 (for sadness), 5 (for anger), 13 (for surprise), and 15 (for disgust) loci exhibited main effects on the recognition of facial expressions. Genetic variations in the dopamine system accounted for 3% for fear, 6% for sadness, 7% for anger, 10% for surprise, and 18% for disgust, with the latter surviving a stringent permutation test. CONCLUSIONS: Genetic variations in the dopamine system (especially the dopamine synthesis and modulation subsystems) made significant contributions to individual differences in the recognition of disgust faces.