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An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson's disease and schizophrenia research.

An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson’s disease and schizophrenia research.

A possible connection between schizotypy and schizophrenia (SZ) might be attributable to their overlapping genetic determinants in terms of the polygenic risk score (PRS). Using multiplex SZ families, this study aims to (1) investigate the relationship of the PRS for SZ (SZ-PRS) and dimensional schizotypal traits, including schizophrenic symptom in the patients with SZ and schizotypy in their unaffected relatives; (2) evaluate the changes of the association patterns of SZ-PRS and dimensional schizotypal traits after combining patients with their unaffected relatives; and (3) examine whether the dimensional schizotypal traits were also associated with PRS for general personality, bipolar disorder (BIP), and major depression disorder (MDD). Among 557 multiplex families recruited in Taiwan Schizophrenia Linkage Study, 1275 individuals were genotyped using Illumina PsychChip array. A total of 538 patients and their 543 unaffected relatives from 315 families, who had passed the quality control and completed the measurements of schizotypal traits, were included for subsequent analyses. A modified Structured Interview for Schizotypy were used for assessing schizotypy factors among unaffected relatives and the Scales for Positive and Negative Symptoms for assessing schizophrenic symptom factors among patients. A PRS was derived first using the summary statistics of the GWAS from the Psychiatric Genomic Consortium-2 SZ cohort as the discovery dataset, and then a weighted sum of SNPs was calculated using the logarithm of each SNP's odds ratio for the effect allele from the discovery dataset. Among the three groups of participants (538 patients, 53 unaffected siblings, and 490 unaffected parents), both patients and unaffected siblings had similar age and educational levels, whereas parents had lower educational levels compared to their offspring. An alignment approach was used to derive the 2-factor schizotypal trait (i.e., the Aligned Positive Schizophrenic-Schizotypy and the Aligned Negative Schizophrenic-Schizotypy factor). We found that the SZ-PRS was correlated only with Disorganization factor from three Schizophrenic symptom factors in the patients as well as with Social isolation/Introversion factor from four Schizotypy factors in their unaffected relatives. Second, after pooling patients and their unaffected relatives, SZ-PRS explained more variance of Aligned Negative Schizophrenic-Schizotypy factor than that of Aligned Positive Schizophrenic-Schizotypy factor. Also, the association effects were slightly increased in the pooled sample compared to that of analyzing patients and unaffected relatives separately. Finally, Aligned Schizophrenic-Schizotypy factors were only associated with SZ-PRS but not with PRS for BIP, MDD, or general personality traits. To our knowledge, this is the first study using multiplex SZ families to exam the association of schizotypal traits (including four Schizotypy factors, three Schizophrenic symptom factors, and two Aligned Schizophrenic-Schizotypy factors) and polygenic risk of SZ. Our findings indicated that SZ-PRS only correlated with specific individual dimension (i.e., Social isolation/Introversion factor) of schizotypy in unaffected relatives of patients with SZ. These results offer support to the hypotheses that the negative dimension of schizotypy reflects more the genetic vulnerability to SZ than the positive dimension of schizotypy. [ABSTRACT FROM AUTHOR]

Background: Administering premixed drugs in commodity packets was first reported in Asia in 2015, but there continues to be a dearth of related population-based data. This study aimed at examining (1) the prevalence of drug-packet use in the population and (2) the sociodemographic profiles, particularly gender distribution, of drug-packet users., Methods: Data were derived from a survey of 18,626 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling in 2018. Participants anonymously completed a computer-assisted self-interview on tablet computers which covered the use and problematic use of illicit drugs/inhalants, prescription drugs, and other psychoactive substances., Results: Approximately 1.46% of respondents had a lifetime use of illicit drugs, with drugs in commodity packets (0.18%) being ranked the fifth-most commonly used illicit drugs, higher than nitrous oxide (0.14%) and heroin (0.09%). Ten formats of drug packets were endorsed by users. Approximately 81.6% of persons with drug packet use had lifetime use of other illicit drugs. The correlates of the use of drugs in commodity packets were different from those of the exclusive use of other drugs, particularly concerning the lack of gender differences in the former category in the whole sample and the subgroups of various sociodemographic characteristics and other substance use., Conclusion: Drugs in commodity packets have become a common way of administering illicit drugs in the population in Taiwan, and there were no gender differences among users. Our findings have implications for more efficient drug testing and culturally appropriate intervention for drug-packet use.

Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression., Competing Interests: None., (AJCR Copyright © 2021.)

This study aimed to examine the multidimensionality of schizotypy and validate the structure using ordered subset linkage analyses on information from both relatives' schizotypy and probands' schizophrenia symptoms. A total of 203 and 1,310 nonpsychotic first-degree relatives from simplex and multiplex schizophrenia families, respectively, were interviewed with the Diagnostic Interview for Genetic Studies, which contains a modified Structured Interview for Schizotypy. Using Mplus program with categorical factor indicators, a four-factor model (Negative Schizotypy, Positive Schizotypy, Interpersonal Sensitivity, and Social Isolation/Introversion) was extracted by exploratory factor analysis from relatives of simplex families and was confirmed in relatives of multiplex families. The validity of each factor was supported by distinct linkage findings resulting from ordered subset analysis based on different combinations of schizophrenia-schizotypy factors. Six chromosomal regions with significant increase in nonparametric linkage z score (NPL-Z) were found as follows: 15q21.1 (NPL-Z = 3.60) for Negative Schizophrenia-Negative Schizotypy, 10q22.3 (NPL-Z = 3.83) and 15q21.3 (NPL-Z = 3.36) for Negative Schizophrenia-Social Isolation/Introversion, 5q14.2 (NPL-Z = 3.20) and 11q23.3 (NPL-Z = 3.31) for Positive Schizophrenia-Positive Schizotypy, and 4q32.1 (NPL-Z = 3.31) for Positive Schizophrenia-Interpersonal Sensitivity. The greatest NPL-Z of 3.83 on 10q22.3 in the subset was significantly higher than the greatest one of 2.88 in the whole sample (empirical P-value = 0.04). We concluded that a consistent four-factor model of schizotypy could be derived in nonpsychotic relatives across families of patients with different genetic loadings in schizophrenia. Their differential relations to linkage signals have etiological implications and provide further evidence for their validity., ((c) 2009 Wiley-Liss, Inc.)