To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets.
TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS.
In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (PPWAS-ROS/MAP = 4.15 × 10−2 and PPWAS-Banner = 3.38 × 10−3) and APOL2 (PPWAS-ROS/MAP = 4.49 × 10−3 and PPWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05).
Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.
Nutrition strongly impacts the incidence and progression of chronic kidney disease (CKD). Recently, reduced rank regression (RRR) has emerged as a method that identifies dietary patterns in an exploratory way while using prior knowledge to select a set of response variables. The aim of this study was to identify a specific dietary pattern associated with renal function using RRR, and to evaluate its association with CKD incidence. We included 78,350 participants from the LifeLines population-based cohort in the Northern Netherlands. All participants were free of CKD (defined as eGFRCKD-EPI < 60 mL/min/1.73 m2) at baseline and completed a second visit four years later. Dietary intake was ascertained with a 110-item food frequency questionnaire. The dietary pattern, stratified by sex, was constructed cross-sectionally by RRR, with eGFR as a response variable. Multivariable logistic regression was used to study the association between dietary patterns score and CKD incidence or an eGFR decline of ≥ 20%, adjusted for potential confounders. Among women, the eGFR-associated dietary pattern was characterized by high intake of eggs, low-fat and high-fat cheese, and legumes and low consumption of sweetened dairy drinks, desserts, cake and cookies, sweet sandwich toppings, white meat, and commercially prepared dishes. The male dietary pattern was characterized by high consumption of high-fat and low-fat cheese, bread, full-fat milk, fruits, vegetables, beer, and low consumption of white and red meat. After a mean follow-up of 3.9 years, 7,612 participants experienced a > 20% eGFR decline and 2,072 participants developed CKD. The eGFR-based diet was associated with a lower risk of eGFR decline (OR 4th vs 1st quartile, women: 0.84 [95% CI 0.76–0.92]; men: 0.74 [0.65–0.84] and of incident CKD (women: 0.60 [0.50–0.73] ; men: 0.52 [0.41–0.66]). The results provide support for potential diet interventions to prevent renal function decline and CKD. RRR may be a useful tool to identify dietary patterns that affect renal function loss and CKD development.
Email your librarian or administrator to recommend adding this to your organisation's collection.