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Background Suicide is the second leading cause of death in young adults, and is accounted for 1.4 percent of all deaths worldwide. More than 90% of suicide attempters or victims had been diagnosed with psychiatric disorders, particularly Major Depressive Disorder (MDD) and Bipolar Disorder (BD). Suicidal behaviour has substantial heritability, however, the underlying etiology of patients diagnosed with different mood disorders may not identical. In the current study, we adopted the Genome-Wide Association Study design (GWAS) to identify genetic variants associated with suicidal behaviors in patients with BD or MDD. Our goal is to identify possible common and unique genetic variants that might be associated to suicidal behavior between the two patient groups. We further test the predictive ability for suicide in the MDD group by using the calculated Polygenic Risk Score (PRS) for suicide in BD patients and vice versa. Methods We recruited 662 BD and 428 MDD patients in Taiwan, who were referred by psychiatrists based on DSM-IV criteria. BD patients were interviewed to collect information of demographic, clinical characteristics, and suicidal behaviors. In addition, the suicide item in Hamilton depression rating scale was used to obtain suicide information for MDD patients. Genotyping was conducted using Affymetrix CHB1 chip for BD, and Illumina Human Omni Express Exome bead chip for MDD with imputation for association analyses. Genetic association and PRS analyses were employed by Plink v1.07. The significance level was set at 5E-08 for adjustment of multiple comparisons, and a p-value less than 1E-06 was considered suggestive association. Results In our samples, 45% of BD and 30% of MDD subjects were male. The onset age for BP and MDD were 18.24 and 38.04 years respectively. The prevalence of suicide attempt was 35% in BD group and 43% in MDD group. There were no loci that reached the genome-wide significance level for suicidal behavior in BP patients. The most significant marker was rs34945506 (p=4.13E-06) located in RCSD1 gene on chromosome 1. In MDD group, marker rs76015177 (p=9.94E-07) showed suggestive association with suicidal behavior. This marker is located on chromosome 9 and is not mapped to any coding gene. There were no common SNPs associated with suicidal behavior in the MDD and BP groups. Discussion Genetic variants that showed suggestive signals with suicidal behavior in the present study were not reported in previous studies. However, due to limited sample size, the power of this study was only moderate, and large-scale replication studies are needed for further validation. One mapped gene, RCSD1, has been reported to regulate the ability of F-actin-capping protein to remodel actin filament assembly via stress-induced phosphorylation. Actin was found to be related to some neurodegeneration diseases, such as Alzheimer's disease. For MDD, two suggestive markers (rs78434258 and rs79070953) on chromosome 9 are found near to the most significant marker (rs76015177) were located on LOC105375976 gene, which is a non-coding RNA. However, the function of this gene is mostly unknown. Lastly, the non-overlapping genetic results for suicidal behaviors in the MDD and BP patients may indicate different pathogenesis and biological pathways for suicide by different diagnosis groups.

Background Seasonal Pattern (SP) was reported in depressive patients of both Bipolar Disorder (BD) and Major Depressive Disorder (MDD). In this study, we aimed to investigate genetic contributions of seasonal pattern of major depressive episodes in both BD and MDD patients, including genes in relevant biological pathways indicated in previous studies. To further clarify the roles of the variants in depression, we conducted analyses using a case-control study design to examine whether the genetic variants for SP also possess effects on susceptibility to depression. Methods We recruited 472 BD (83%) and MDD (17%) patients in Taiwan. SP of depressive episode were defined according to interview questions as “Which season do you feel the worst?” in their first, the most serious, and the most recent episode within a year. Subjects answered a specific season in two of the three episode categories were considered SP+, while others were categorized as non-SP (SP-). The other dataset for depression was obtained from the Taiwan biobank with about 10,000 people. Cases were defined by self-report MDD history or having the sum-score greater than 3 in the Patient Health Questionnaire-4. We examined 15 genes (824 single nucleotide variants) including the melatonin pathway (MTNR1a, MTNR1b, AANAT), serotonin pathway (TPH2, HTR2A, HTR2B, SLC6A4), circadian feedback loop (NPAS2, CRY2, ARNTL, ARNTL2, RORA, RORB, PER) and NF1A gene that identified from a previous genome-wide association study of seasonal mania. Association analyses were performed by multivariate logistic regression, adjusting for gender, age, and diagnosis. We corrected for multiple testings using false discovery rate method. Results After excluding subjects with missing covariates, there were a total of 464 subjects with 162 (35%) in the SP+ and 302 (65%) in the SP- groups. No differences were observed in gender, age or diagnosis distribution between the two SP groups. Nominal associations with p-value The 20 markers were tested again for depression in 9862 individuals from Taiwan biobank. Although none of them showed genome-wide significance, 6 SNPs had nominal p-values Discussion We found that NF1A gene maybe a susceptible gene for depression and modifiable gene for SP. Some genetic variants in this gene are related to both seasonal pattern of depressive episodes and depression with nominal significance, indicating partially shared genetic components between the development of mood symptoms and seasonality in depression. Further investigation is needed for replication with more stringent seasonal pattern evaluation, and for exploring the exact biological functions of the identified genetic variants.

Background Peptic ulcer is a common yet serious disease affected about 4 million people worldwide. Depression is considered a risk factor for peptic ulcer and may modify the etiology underlying peptic ulcer. Genetic factors contribute on the risk of developing peptic ulcer, but it remains unclear whether the genetic influences differ between depressed and non-depressed groups. In this study, we conducted genome-wide association studies for peptic ulcer stratified by depression status in Taiwanese samples. Methods Subjects in this study were drawn from Taiwan biobank with detailed demographic and clinical data collection. A total of 10,295 individuals were initially included, and 9,862 participants were retained after quality control, which consisted of 1,218 (12%) depression individuals based on prior diagnosis of major depressive disorder or high scores of self-report patient health questionnaire for depression and anxiety (scores greater than 3). Genetic association analyses were performed using logistic regression models while adjusted for age and sex. A p-value less than 10-5 was considered with suggestive association signals. Results Within depressed group, the top three associated SNPs were rs4775785 (P-value=1.20×10-7), rs10162880 (P=4.38×10-7) and rs7177833 (P=5.17×10-7). After gene mapping, these top SNPs were all map to the SHC4 gene, a protein coding gene on chromosome 15. In the non-depressed group, a different set of associated SNPs were observed, with rs11238817 (P=2.16×10-6) and rs11637781(P=4.41×10-6) showing suggestive signals without mapped to known coding genes. Discussion There is no overlapping markers or genes for peptic ulcer between the depressed and non-depressed groups, indicating different genetic profiles among the two groups. A replication study is needed with larger sample size, especially for the identified gene located on chromosome 15 in depressed individuals.

Background Major depressive disorder (MDD) is a complex and multifactorial disorder with heterogeneous syndromal presentations. Patients’ response to commonly prescribed selective serotonin reuptake inhibitors (SSRIs) varies across individuals and symptoms. Certain genetic variants may modify the effects of SSRIs treatment on different symptoms. Methods We recruited patients with a diagnosis of MDD from two central hospitals in Taiwan, who were treated with escitalopram (38.5 %), paroxetine (38.5%), fluoxetine (18.3%), and citalopram (4.8%). Depression severity was rated using the 21-item Hamilton Rating Scale for Depression (HRSD) in all participants, with a minimum score of 14 at baseline for inclusion. Patients were assessed repeatedly at week 2, 4, and 8. All participants were genotyped using Illumina HumanOmniExpressExome BeadChips in the International SSRI Pharmacogenomics Consortium. After quality controls, 421 patients (mean age of 43.7 years and 71% of females) with 4,241,701 genotyped and well-imputed SNPs were retained for analysis. We first performed exploratory factor analysis to identify latent syndromal factors for baseline HRSD. Treatment response was defined for two variables: score change (score difference between baseline and week-4, divided by the total score in each factor – scaling to range between 0-1), and binary response (⩾50% score reduction from baseline to week-4). Linear and logistic regression models were used for association testing while adjusted for age and sex. Results We obtained six empirically derived factors for HRSD, namely sleep, core, anxiety, somatization, psychomotor, and energy. The degree of improvement in syndromal severity at week-4 was ranged from 33% (energy) to 70% (psychomotor). No markers reached genome-wide significance level. Nevertheless, several loci showed suggestive signals with p-value Discussion We found several genes that might affect treatment response of different empirically defined syndromal factors among SSRIs treated depression patients. Further replication studies are needed to confirm our findings in other populations.