Identification of novel Carnobacterium maltaromaticum strains in bone marrow samples of patients with acute myeloid leukemia using a metagenomic binning approach.

The aim of this study aimed to examine the existence of a bacterial metagenome in the bone marrow of patients with acute myeloid leukemia (AML). We re-examined whole-genome sequencing data from the bone marrow samples of seven patients with AML, four of whom were remitted after treatment, for metagenomic analysis. After the removal of human reads, unmapped reads were used to profile the species-level composition. We used the metagenomic binning approach to confirm whether the identified taxon was a complete genome of known or novel strains. We observed a unique and novel microbial signature in which Carnobacterium maltaromaticum was the most abundant species in five patients with AML or remission. The complete genome of C. maltaromaticum "BMAML_KR01," which was observed in all samples, was 100% complete with 8.5% contamination and closely clustered with C. maltaromaticum strains DSM20730 and SF668 based on single nucleotide polymorphism variations. We identified five unique proteins that could contribute to cancer progression and 104 virulent factor proteins in the BMAML_KR01 genome. To our knowledge, this is the first report of a new strain of C. maltaromaticum in patients with AML. The presence of C. maltaromaticum and its new strain in patients indicates an urgent need to validate the existence of this bacterium and evaluate its pathophysiological role.

Association Between Gut Microbiota and Depressive Symptoms: A Cross-Sectional Population-Based Study in South Korea.

OBJECTIVE: This study aimed to investigate the association between gut microbiota and depressive symptoms in a large population cohort of Korean adults. METHODS: Overall, 1238 participants were included in the study. Participants were categorized into depressed or non-depressed groups, based on the depressive symptoms reported on the Center for Epidemiologic Studies Rating Scale for Depression, with a cutoff score of 16, and their fecal microbiota was profiled using 16S ribosomal RNA gene sequencing. Several alpha and beta diversity measures were also estimated. The association between depressive symptoms and gut microbiota was analyzed using generalized linear models. The inferred function of the metagenomes was compared between the two groups. RESULTS: There were no consistent differences in alpha and beta diversity between the depressed and non-depressed groups. However, the continuous measure of depressive symptoms was inversely associated with one of four measures of alpha diversity (Shannon's diversity, p = .021). We also found a substantial difference between the depressed and non-depressed groups in the Bray-Curtis dissimilarity among the four beta diversity indices ( p = .004). Participants whose depressive symptoms exceeded a clinical cutoff score had a lower relative abundance of the genus Faecalibacterium when compared with controls (coefficient = -0.025, q = 0.047). However, the depressed group had a significantly higher abundance of the genus Oscillospira than did the non-depressed group (coefficient = 0.002, q = 0.023). CONCLUSIONS: Our findings contribute to the identification of potential relationships between the gut microbiota and depressive symptoms and provide useful insights for developing microbiota-based interventions for patients with depressive symptoms.

Development of the variant calling algorithm, ADIScan, and its use to estimate discordant sequences between monozygotic twins.

Calling variants from next-generation sequencing (NGS) data or discovering discordant sequences between two NGS data sets is challenging. We developed a computer algorithm, ADIScan1, to call variants by comparing the fractions of allelic reads in a tester to the universal reference genome. We then created ADIScan2 by modifying the algorithm to directly compare two sets of NGS data and predict discordant sequences between two testers. ADIScan1 detected >99.7% of variants called by GATK with an additional 724 393 SNVs. ADIScan2 identified ∼500 candidates of discordant sequences in each of two pairs of the monozygotic twins. About 200 of these candidates were included in the ∼2800 predicted by VarScan2. We verified 66 true discordant sequences among the candidates that ADIScan2 and VarScan2 exclusively predicted. ADIScan2 detected many discordant sequences overlooked by VarScan2 and Mutect, which specialize in detecting low frequency mutations in genetically heterogeneous cancerous tissues. Numbers of verified sequences alone were >5 times more than expected based on recently estimated mutation rates from whole genome sequences. Estimated post-zygotic mutation rates were 1.68 × 10-7 in this study. ADIScan1 and 2 would complement existing tools in screening causative mutations of diverse genetic diseases and comparing two sets of genome sequences, respectively.

Oncogenic effects of germline variants in lysosomal storage disease genes.

PURPOSE: Clinical and experimental evidence has suggested pathobiological crosstalk between lysosomal storage diseases (LSDs) and cancer. We aimed to elucidate the association between germline variants in LSD genes and cancer. METHODS: We performed aggregate rare variant association analysis of potentially pathogenic variants (PPVs) in 42 LSD genes and >30 histological types of cancer using genome sequencing data from 2567 cancer patients (Pan-Cancer cohort) and 2504 healthy individuals (1000 Genomes cohort) and exome sequencing data from 53,105 individuals without cancer (ExAC cohort). RESULTS: PPVs were significantly enriched in the Pan-Cancer cohort compared with the 1000 Genomes cohort (PPV prevalence, 20.7% vs. 13.5%; P = 8.7 × 10-12). Cancer risk was higher in individuals with a greater number of PPVs (P = 7.3 × 10-12). Population structure-adjusted optimal sequence kernel association test (SKAT-O) revealed 37 significantly associated cancer type-LSD gene pairs. These results were supported by the consistent tendency toward enrichment of PPVs in cancer patients compared with the ExAC cohort. Cancer developed earlier in PPV carriers than in wild-type patients. Analysis of tumor transcriptomic data from the pancreatic adenocarcinoma cohort revealed 508 genes differentially expressed according to PPV carrier status, which were highly enriched in the core signaling pathways of pancreatic cancer. CONCLUSION: Carriers of PPVs in LSD genes are at increased risk of cancer.

Fecal Microbiota Differences According to the Risk of Advanced Colorectal Neoplasms.

GOALS AND BACKGROUND: This study aimed to compare differences in the fecal microbiota according to the risk of advanced colorectal neoplasia (ACN) based on a risk-score model in a large Korean cohort. STUDY: Stool samples were collected from 1122 health screening recipients: 404 enrolled in the average risk (AR) group, 514 in the moderate risk (MR) group, and 204 in the high risk (HR) group, in accordance with their risk of ACN. The fecal microbiota was characterized using pyrosequencing of the V3-V4 region of the 16S rRNA genes. RESULTS: The overall microbial diversity was significantly reduced with an increased risk of ACN [false discovery rate (FDR), P<0.001], and the composition was significantly different between the risk groups (Bonferroni corrected, P<0.05). On taxonomic comparison, 6 of 11 phyla and 39 of 88 genera were significantly different among the risk groups (all FDR P<0.05). These included under-representation of Bacteroides, Ruminococcus, and Bifidobacterium, and over-representation of Prevotella and Fusobacterium with an increased risk of ACN. In particular, we observed that the unknown genus of Ruminococcaceae were relatively abundant (16.2%) in the AR group and significantly depleted with an increased risk of ACN (13.5% in the HR group; FDR P<0.001). CONCLUSIONS: These findings support the hypothesis that the fecal microbiota is different according to the risk of ACN. An unknown genus of Ruminococcaceae, as novel potential butyrate producers, might have a possible role in colorectal tumorigenesis in the Korean population.

Integrated genome sizing (IGS) approach for the parallelization of whole genome analysis.

BACKGROUND: The use of whole genome sequence has increased recently with rapid progression of next-generation sequencing (NGS) technologies. However, storing raw sequence reads to perform large-scale genome analysis pose hardware challenges. Despite advancement in genome analytic platforms, efficient approaches remain relevant especially as applied to the human genome. In this study, an Integrated Genome Sizing (IGS) approach is adopted to speed up multiple whole genome analysis in high-performance computing (HPC) environment. The approach splits a genome (GRCh37) into 630 chunks (fragments) wherein multiple chunks can simultaneously be parallelized for sequence analyses across cohorts. RESULTS: IGS was integrated on Maha-Fs (HPC) system, to provide the parallelization required to analyze 2504 whole genomes. Using a single reference pilot genome, NA12878, we compared the NGS process time between Maha-Fs (NFS SATA hard disk drive) and SGI-UV300 (solid state drive memory). It was observed that SGI-UV300 was faster, having 32.5 mins of process time, while that of the Maha-Fs was 55.2 mins. CONCLUSIONS: The implementation of IGS can leverage the ability of HPC systems to analyze multiple genomes simultaneously. We believe this approach will accelerate research advancement in personalized genomic medicine. Our method is comparable to the fastest methods for sequence alignment.

Rosacea and its association with enteral microbiota in Korean females.

Rosacea is a chronic inflammatory dermatosis affecting the face and eyes. An association between systemic comorbidities and rosacea has been reported, but the link to enteral microbiota is uncertain. We aimed to investigate the link between rosacea and enteral microbiota. A cross-sectional study was performed in a sample of Korean women who participated in a health check-up programme at the Kangbuk Samsung Hospital Health Screening Center between 23 June 2014 and 5 September 2014. The gut microbiome was evaluated by 16S rRNA gene and metagenome sequence analyses. A total of 12 rosacea patients and 251 controls were enrolled. We identified links between rosacea and several changes in gut microbiota: reduced abundance of Peptococcaceae family unknown genus, Methanobrevibacter (genus), Slackia (genus), Coprobacillus (genus), Citrobacter (genus), and Desulfovibrio (genus), and increased abundance of Acidaminococcus (genus), Megasphaera (genus), and Lactobacillales order unknown family unknown genus. A link between rosacea and enteral microbiota was observed in this metagenomic study. A large and elaborate study is needed to confirm these findings and to elucidate the mechanisms involved.

Correlation between gut microbiota and personality in adults: A cross-sectional study.

Personality affects fundamental behavior patterns and has been related with health outcomes and mental disorders. Recent evidence has emerged supporting a relationship between the microbiota and behavior, referred to as brain-gut relationships. Here, we first report correlations between personality traits and gut microbiota. This research was performed using the Revised NEO Personality Inventory and the sequencing data of the 16S rRNA gene in 672 adults. The diversity and the composition of the human gut microbiota exhibited significant difference when stratified by personality traits. We found that personality traits were significantly correlated with diversity of gut microbiota, while their differences were extremely subtle. High neuroticism and low conscientiousness groups were correlated with high abundance of Gammaproteobacteria and Proteobacteria, respectively when covariates, including age, sex, BMI and nutrient intake, were controlled. Additionally, high conscientiousness group also showed increased abundance of some universal butyrate-producing bacteria including Lachnospiraceae. This study was of observational and cross-sectional design and our findings must be further validated through metagenomic or metatranscriptomic methodologies, or metabolomics-based analyses. Our findings will contribute to elucidating potential links between the gut microbiota and personality, and provide useful insights toward developing and testing personality- and microbiota-based interventions for promoting health.

HLAscan: genotyping of the HLA region using next-generation sequencing data.

BACKGROUND: Several recent studies showed that next-generation sequencing (NGS)-based human leukocyte antigen (HLA) typing is a feasible and promising technique for variant calling of highly polymorphic regions. To date, however, no method with sufficient read depth has completely solved the allele phasing issue. In this study, we developed a new method (HLAscan) for HLA genotyping using NGS data. RESULTS: HLAscan performs alignment of reads to HLA sequences from the international ImMunoGeneTics project/human leukocyte antigen (IMGT/HLA) database. The distribution of aligned reads was used to calculate a score function to determine correctly phased alleles by progressively removing false-positive alleles. Comparative HLA typing tests using public datasets from the 1000 Genomes Project and the International HapMap Project demonstrated that HLAscan could perform HLA typing more accurately than previously reported NGS-based methods such as HLAreporter and PHLAT. In addition, the results of HLA-A, -B, and -DRB1 typing by HLAscan using data generated by NextGen were identical to those obtained using a Sanger sequencing-based method. We also applied HLAscan to a family dataset with various coverage depths generated on the Illumina HiSeq X-TEN platform. HLAscan identified allele types of HLA-A, -B, -C, -DQB1, and -DRB1 with 100% accuracy for sequences at ≥ 90× depth, and the overall accuracy was 96.9%. CONCLUSIONS: HLAscan, an alignment-based program that takes read distribution into account to determine true allele types, outperformed previously developed HLA typing tools. Therefore, HLAscan can be reliably applied for determination of HLA type across the whole-genome, exome, and target sequences.

Identification of somatic mutations using whole-exome sequencing in Korean patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous cancer of the bone marrow that is characterized by the rapid growth of abnormal myeloid cells. METHODS: We performed a mutational analysis to identify AML somatic mutations using the whole-exome sequencing data of 36 tumor-normal sample pairs from Korean patients with de novo AML. We explored the functional impact of the genes identified in the mutational analyses through an integrated Gene Ontology (GO) and pathway analysis. RESULTS: A total of 11 genes, including NEFH (p = 6.27 × 10-13 and q = 1.18 × 10-8) and TMPRSS13 (p = 1.40 × 10-10 and q = 1.32 × 10-6), also demonstrated q values less than 0.1 in 36 Korean AML patients. Five out of the 11 novel genes have previously been reported to be associated with other cancers. Two gene mutations, CEBPA (p = 5.22 × 10-5) and ATXN3 (p = 9.75 × 10-4), showed statistical significance exclusively in the M2 and M3 subtypes of the French-American-British classifications, respectively. A total of 501 genes harbored 478 missense, 22 nonsense, 93 frameshift indels, and/or three stop codon deletions and these gene mutations significantly enriched GO terms for signal transduction (GO:0007165, p = 1.77 × 10-3), plasma membrane (GO:0005886, p = 3.07 × 10-4), and scaffold protein binding (GO:0097110, p = 8.65 × 10-4). The mitogen-activated protein kinase (hsa04010, 7.67 × 10-4) was the most enriched Kyoto Encyclopedia of Genes and Genomes pathway. CONCLUSIONS: Morphological AML subtypes may in part reflect subtype specific patterns of genomic alterations. Following validation, future studies to evaluate the usefulness of these genes in genetic testing for the early diagnosis and prognostic prediction of AML patients would be worthwhile.

Comparative analysis of gut microbiota associated with body mass index in a large Korean cohort.

BACKGROUND: Gut microbiota plays an important role in the harvesting, storage, and expenditure of energy obtained from one's diet. Our cross-sectional study aimed to identify differences in gut microbiota according to body mass index (BMI) in a Korean population. 16S rRNA gene sequence data from 1463 subjects were categorized by BMI into normal, overweight, and obese groups. Fecal microbiotas were compared to determine differences in diversity and functional inference analysis related with BMI. The correlation between genus-level microbiota and BMI was tested using zero-inflated Gaussian mixture models, with or without covariate adjustment of nutrient intake. RESULTS: We confirmed differences between 16Sr RNA gene sequencing data of each BMI group, with decreasing diversity in the obese compared with the normal group. According to analysis of inferred metagenomic functional content using PICRUSt algorithm, a highly significant discrepancy in metabolism and immune functions (P < 0.0001) was predicted in the obese group. Differential taxonomic components in each BMI group were greatly affected by nutrient adjustment, whereas signature bacteria were not influenced by nutrients in the obese compared with the overweight group. CONCLUSIONS: We found highly significant statistical differences between normal, overweight and obese groups using a large sample size with or without diet confounding factors. Our informative dataset sheds light on the epidemiological study on population microbiome.

Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism.

Neuroticism is a heritable personality trait that is comprised of distinct sub-factors, or facets. Sub-factors of neuroticism are linked to different emotional states or psychiatric symptoms and studying the genetic variants associated with these facets may help reveal the biological mechanisms underlying psychiatric disorders. In the present study, a meta-analysis of genome-wide association studies for six facets of neuroticism was performed in 5584 participants from three cohorts. Additionally, a Gene Set Enrichment Analysis was conducted to find biological pathways associated with each facet. Six neuroticism facets (N1: anxiety, N2: angry hostility, N3: depression, N4: self-consciousness, N5: impulsivity and N6: vulnerability) were assessed using the Korean version of the Revised NEO Personality Inventory. In the single-nucleotide polymorphism-based analysis, results showed genome-wide significance for N2 within the MIR548H3 gene (rs1360001, P=4.14 × 10-9). Notable genes with suggestive associations (P<1.0 × 10-6) were ITPR1 for N1, WNT7A for N2, FGF10 and FHIT for N3, DDR1 for N4, VGLL4 for N5 and PTPRD for N6. In the pathway-based analysis, the axon guidance pathway was identified to be associated with multiple facets of neuroticism (N2, N4 and N6). The focal adhesion and extracellular matrix receptor interaction pathways were significantly associated with N2 and N3. Our findings revealed genetic influences and biological pathways that are associated with facets of neuroticism.

Cytidine deaminase polymorphisms and worse treatment response in normal karyotype AML.

The cytidine deaminase (CDA) catalyzes the irreversible hydrolytic deamination of the cytarabine (AraC) into a 1-ß-D-arabinofuranosyluracil (AraU), an inactive metabolite that plays a crucial role in lowering the amount of AraC, a key chemotherapeutic drug, in the treatment of patients with acute myeloid leukemia (AML). In this study, we hypothesized that CDA polymorphisms were associated with the AraC metabolism for AML treatment and/or related clinical phenotypes. We analyzed 16 polymorphisms of CDA among 50 normal karyotype AML (NK-AML) patients, 45 abnormal karyotype AML (AK-AML) patients and 241 normal controls (NC). Several polymorphisms and haplotypes, rs532545, rs2072671, rs471760, rs4655226, rs818194 and CDA-ht3, were found to have a strong correlation with NK-AML compared with NC and these polymorphisms also revealed strong linkage disequilibrium with each other. Among them, rs2072671 (79A>C), which is located in a coding region and the resultant amino acid change K27Q, showed significant associations with NK-AML compared with NC (P=0.009 and odds ratio=2.44 in the dominant model). The AC and CC genotypes of rs2072671 (79A>C) were significantly correlated with shorter overall survival rates (P=0.03, hazard ratio=1.84) and first complete remission duration (P=0.007, hazard ratio=3.24) compared with the AA genotype in the NK-AML patients. Our results indicate that rs2072671 in CDA may be an important prognostic marker in NK-AML patients.

GWA meta-analysis of personality in Korean cohorts.

Personality is a determinant of behavior and lifestyle that is associated with health and human diseases. Despite the heritability of personality traits is well established, the understanding of the genetic contribution to personality trait variation is extremely limited. To identify genetic variants associated with each of the five dimensions of personality, we performed a genome-wide association (GWA) meta-analysis of three cohorts, followed by comparison of a family cohort. Personality traits were measured with the Revised NEO Personality Inventory for the five-factor model (FFM) of personality. We investigated the top five single-nucleotide polymorphisms (SNPs) for each trait, and revealed the most highly association with neuroticism and TACC2 (rs1010657, P=8.79 × 10(-7)), extraversion and PTPN12 (rs12537271, P=1.47 × 10(-7)), openness and IMPAD1 (rs16921695, P=5 × 10(-8)), agreeableness and RPS29 (rs8015351, P=1.27 × 10(-6)) and conscientiousness and LMO4 (rs912765, P=2.91 × 10(-6)). It had no SNP reached the GWA study threshold (P<5 × 10(-8)). When expanded the SNPs up to top 100, the correlation of PTPRD (rs1029089) and agreeableness was confirmed in Healthy Twin cohort with other 13 SNPs. This GWA meta-analysis on FFM personality traits is meaningful as it was the first on a non-Caucasian population targeted to FFM of personality traits.

Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome.

STUDY QUESTION: Are there any novel genetic markers of susceptibility to polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: We identified a novel susceptibility locus on chromosome 8q24.2 and several moderately associated loci for PCOS in Korean women. WHAT IS KNOWN ALREADY: PCOS is a highly complex disorder with significant contributions from both genetic and environmental factors. Previous genome-wide association studies (GWAS) in the Han Chinese population identified several risk loci for PCOS. However, GWAS studies on PCOS remain very few. The aim of this study was to identify novel markers of susceptibility to PCOS through GWAS. STUDY DESIGN, SIZE, DURATION: A two-stage GWAS was conducted. The initial discovery set for GWAS consisted of 976 PCOS cases and 946 controls. The second stage (replication study) included 249 PCOS cases and 778 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were diagnosed according to the Rotterdam criteria. Genomic DNAs were genotyped using the HumanOmni1-Quad v1 array. In the replication stage, the 21 most promising signals selected from the discovery stage were tested for their association with PCOS. MAIN RESULTS AND THE ROLE OF CHANCE: One novel locus with genome-wide significance and seven moderately associated loci for PCOS were identified. The strongest association was on chromosome 8q24.2 (rs10505648, OR = 0.52, P = 5.46 × 10(-8)), and other association signals were located at 4q35.2, 16p13.3, 4p12, 3q26.33, 9q21.32, 11p13 and 1p22 (P = 5.72 × 10(-6)-6.43 × 10(-5)). The strongest signal was located upstream of KHDRBS3, which is associated with telomerase activity, and could drive PCOS and related phenotypes. LIMITATIONS, REASONS FOR CAUTION: The limitation of our study is the modest sample size used in the replication cohort. The limited sample size may contribute to a lack of statistical power to detect an association or show a trend in severity. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide new insight into the genetics and biological pathways of PCOS and could contribute to the early diagnosis and prevention of metabolic and reproductive morbidities. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by the grant from the Korea Centers for Disease Control and Prevention (2009-E00591-00). The work was also supported by the Ewha Global Top5 Grant 2013 of Ewha Womans University. None of the authors has any conflict of interest to declare.

Trends in clinical outcomes of older hemodialysis patients: data from the 2023 Korean Renal Data System (KORDS).

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

Mortality in patients receiving renal replacement therapy in South Korea.

Background: This study analyzed data from the end-stage renal disease patient registry collected by the Korean Society of Nephrology to explore trends in mortality among dialysis patients from 2001 to 2022. Methods: Mortality was analyzed in two ways: firstly, using the annual mortality rate; and secondly, by assessing survivability after a certain period of time since the initiation of dialysis. Additionally, we categorized the causes of death by disease group annually to observe how the proportions changed. Results: Since 2001, annual mortality for dialysis patients generally declined, except for a rise in 2020 and 2021 among hemodialysis patients. Overall mortality rates for all dialysis patients dropped from 74.2/1,000 person-years in 2001 to 42.3/1,000 person-years in 2022, with a more pronounced decrease in peritoneal dialysis. While survival probability over the 5 years following initiation of dialysis has shown a steady increase, short-term mortality from 2018 to 2020 affected by coronavirus disease 2019 (COVID-19) has shown a yearly increase by age group, with a greater effect in those aged 75 years and older. The leading causes of death for all dialysis patients have changed little, in the order of heart disease, infection, and vascular problems. Conclusion: While annual mortality and survival probability after dialysis initiation have generally improved in dialysis patients, there has been a temporary deterioration during the COVID-19 pandemic, most pronounced in the elderly.

Genome-wide association study of the five-factor model of personality in young Korean women.

Personality is a determinant of behavior and lifestyle associated with health and human diseases. Although personality is known to be a heritable trait, its polygenic nature has made the identification of genetic variants elusive. We performed a genome-wide association study on 1089 Korean women aged 18-40 years whose personality traits were measured with the Revised NEO Personality Inventory for the five-factor model of personality. To reduce environmental factors that may influence personality traits, this study was restricted to young adult women. In the discovery phase, we identified variants of PTPRD (protein tyrosine phosphatase, receptor type D) that associated this gene with the Openness domain. Other genes that were previously reported to be associated with neurological phenotypes were also associated with personality traits. In particular, DRD1 and OR1A2 were linked to Neuroticism, NKAIN2 with Extraversion, HTR5A with Openness and DRD3 with Agreeableness. Data from our replication study of 2090 subjects confirmed the association between OR1A2 and Neuroticism. We first identified and confirmed a novel region on OR1A2 associated with Neuroticism [corrected]. Candidate genes for psychiatric disorders were also enriched. These findings contribute to our understanding of the genetic architecture of personality traits and provide critical clues to the neurobiological mechanisms that influence them.