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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
The spectra of the Sloan Digital Sky Survey (SDSS) are being used to construct a catalogue of QSO absorption lines, for use in studies of abundances, relevant radiation fields, number counts as a function of redshift, and other matters, including the evolution of these parameters. The catalogue includes intervening, associated, and BAL absorbers, in order to allow a clearer definition of the relationships between these three classes. We describe the motivation for and the data products of the project to build the SDSS QSO absorption line catalogue.
The chloride bearing corrosion product akaganéite (βFeOOH) can form during postexcavation corrosion of chloride infested archaeological iron and is able to corrode iron in contact with it. Its action on iron is examined using βFeOOH synthesized from ferrous chloride and iron powder. Using weight measurements the hygroscopicity of βFeOOH is established. The influence of relative humidity on the corrosion of iron powder mixed with βFeOOH is examined by dynamic mass change within a climatic chamber. At 20°C and 12% relative humidity, iron in contact with βFeOOH did not corrode. At 15% relative humidity slight iron corrosion was detected after 160 hours, but at 35% relative humidity corrosion occurred after a few hours. Surface adsorbed chloride was removed from βFeOOH by aqueous washing and this reduced its hygroscopicity. The reported metastability of βFeOOH was examined via XRD of a 23 year old sample, which was found to be still entirely composed of βFeOOH. These results provide better understanding of βFeOOH corrosion of iron, corrosion control of chloride infested iron using dry storage and the effect of aqueous washing on archaeological iron.
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