No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Harmonization and standardization of nucleus pulposus cell extraction and culture methods

Background In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re-differentiation media and techniques were also investigated. Results Recommended protocols are provided for extraction, expansion, and re-differentiation of NP cells from common species utilized for NP cell culture. Conclusions This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species-specific pronase usage, 60–100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross-lab comparisons on NP cells worldwide

Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen.Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.Peer reviewe

Sorption potential of oil palm shell for the removal of chlorinated phenol from aqueous solution:Kinetic investigation

In this study, activated carbons (ACs) from oil palm shell (OPS) were prepared using the two-stage self-generated atmosphere method, comprising of a semi-carbonization stage and a chemical activation stage, which were fixed at 300°C and 500°C respectively. The prepared adsorbents were tested in the removal of 2,4-dichlorophenol (2,4-DCP) from aqueous solution. The samples were impregnated by varying the zinc chloride (ZnCl2) to precursor (OPS) ratio, after which, the final products, ACs, underwent several aspects of chemical and physical characterizations, i.e. percentage of yield, moisture content, ash content, pH, porosity, adsorption kinetics and isotherms (2,4-DCP) and surface chemistry of the adsorbent. The results indicated that the percentage of yield, moisture content and ash content had increased in proportional to the increase in ZnCl2 ratio. It was found that AC4, with the impregnation ration of 1:4 (OPS:ZnCl2) had the highest adsorption capacity of 26.40 mg/g. While the maximum Brunauer, Emmett and Teller (BET) surface area of AC4 was found to be around 1020 m2/g. Adsorption studies indicated an increased in adsorption capacity in proportional to the increase in adsorbate initial concentration and adsorbent dosage, whereas a higher pH decreased the adsorption capacity. The adsorption isotherm of all the prepared ACs fitted well to the Langmuir model, while the sorption kinetics followed the pseudo-second order, indicating that the adsorption was a single layer chemisorption process

Mechanical and morphological properties of PP/LLPDE/NR blends-effect of polyoctenamer

In this study, impact-modified polypropylene (PP) ternary blends based on PP/natural rubber (NR)/linear low-density polyethylene (LLDFE) with ratios of 72/10/18 and 64/20/16 were produced by a twin-screw extruder with polyoctenamer (TOR) as the compatibilizer. The mechanical properties of the blend were determined on injection-molded specimens in tensile, flexural, and impact testing. The impact strength and elongation at break of the blend increased significantly while the flexural modulus and tensile strength decreased slightly with increasing TOR content. The impact strength improved with the increasing TOR due the increase of interfacial adhesion resulting in finer dispersion of the rubbery minor phase in the PP matrix. The improvement in compatibility with the addition of TOR into PP/NR/LLDPE blends is being supported by both scanning electron microscopy (SEM) and dynamic mechanical analysis (DMA)