scholarly journals Causal effect of C-reactive protein and vitamin D on human cerebral anatomy observed among genetically correlated biomarkers in blood

Author(s):  
Dylan James Kiltschewskij ◽  
William R Reay ◽  
Murray J Cairns

Psychiatric disorders such as schizophrenia are commonly associated with structural brain alterations affecting the cortex, which frequently vary with clinically relevant factors including antipsychotic treatment, duration of illness and age of onset. While the underlying variables mediating these structural changes are poorly understood, recent genetic evidence suggests circulating metabolites and other biochemical traits play a causal role in a number of psychiatric disorders which could be mediated by changes in the cerebral cortex. In the current study, we leveraged publicly available genome-wide association study (GWAS) data to explore shared genetic architecture and evidence for causal relationships between a panel of 50 biochemical traits and measures of cortical thickness and surface area at both the global and regional levels. Linkage disequilibrium score regression identified a total of 20 significant and 156 suggestive genetically correlated biochemical-cortical trait pairings, of which six exhibited strong evidence for causality in a latent causal variable model. Interestingly, a negative causal relationship was identified between a unit increase in serum C-reactive protein levels and thickness of the lingual and lateral occipital regions that was also supported by Mendelian randomisation, while circulating vitamin D (25-hydroxyvitamin D) levels exhibited a positive causal effect on temporal pole thickness. Taken together, our findings suggest a subset of biochemical traits exhibit shared genetic architecture and potentially causal relationships with cortical thickness in functionally distinct regions, which may contribute to alteration of cortical structure in psychiatric disorders.

2021 ◽  
Author(s):  
William R Reay ◽  
Dylan J Kiltschewskij ◽  
Michael P Geaghan ◽  
Joshua R Atkins ◽  
Vaughan J Carr ◽  
...  

There is a long-standing interest in exploring the relationship between blood-based biomarkers of biological exposures and psychiatric disorders, despite their causal role being difficult to resolve in observational studies. In this study, we leverage genome-wide association study data for a large panel of heritable biochemical traits measured from serum to refine our understanding of causal effect in biochemical-psychiatric trait parings. In accordance with expectation we observed widespread evidence of positive and negative genetic correlation between psychiatric disorders and biochemical traits. We then implemented causal inference to distinguish causation from correlation and found strong evidence that C-reactive protein (CRP) exerts a causal effect on psychiatric disorders, along with other putatively causal relationships involving urate and glucose. Strikingly, these analyses suggested CRP has a protective effect on three disorders including anorexia nervosa, obsessive-compulsive disorder, and schizophrenia, whilst being a risk factor for major depressive disorder. Multivariable models that conditioned CRP effects on interleukin-6 signalling and body mass index suggested that CRP-schizophrenia relationship was not likely mediated by those factors. Collectively, these data suggest that there are shared pathways that influence both biochemical traits and psychiatric illness, including factors such as CRP that are likely to constitute a causal effect and could be targets for therapeutic intervention and precision medicine.


2018 ◽  
Vol 14 (2) ◽  
pp. 105-128
Author(s):  
Giordano Padovan ◽  
Rosa Preteroti ◽  
Beatrice Bortolato ◽  
Maria Magdalini Papaioannou ◽  
Giada Piva ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2780
Author(s):  
Andrzej Krajewski ◽  
Krzysztof Piorun ◽  
Dominika Maciejewska-Markiewicz ◽  
Marta Markowska ◽  
Karolina Skonieczna-Żydecka ◽  
...  

Background: Burned patients have an increased need for vitamin D supply related to the maintenance of calcium–phosphate homeostasis and the regulation of cell proliferation/differentiation. This study aimed to analyze the concentration of 25-hydroxycholecalciferol and its relationship with severe condition after burn injury. Methods: 126 patients were enrolled in the study. Patients were qualified due to thermal burns—over 10% of total body surface area. On the day of admission, the following parameters were assessed: 25-hydroxycholecalciferol concentration, total protein concentration, albumin concentration, aspartate transaminase activity, alanine transaminase activity, albumin concentration, creatinine concentration, c-reactive protein concentration, procalcitonin concentration, and interleukin-6 concentration. Results: Almost all patients (92%) in the study group had an improper level of vitamin D (<30 ng/mL), with the average of 11.6 ± 10.7 ng/mL; 17.5% of patients had levels of vitamin D below the limit of determination—under 3 ng/mL. The study showed that there are several factors which correlated with vitamin D concentration during the acute phase of burn injury, including: total protein (r = 0.42, p < 0.01), albumin, (r = 0.62, p < 0.01), percentage of body burns (r = 0.36, p < 0.05), aspartate aminotransferase (r = 0.21, p < 0.05), and c-reactive protein (r = 0.22, p < 0.05). We did not find any significant correlation between vitamin D concentration and body mass index. Conclusions: The burn injury has an enormous impact on the metabolism and the risk factors of the deficiency for the general population (BMI) have an effect on burned patients. Our study showed that concentration of 25-hydroxycholecalciferol is strongly correlated with serum albumin level, even more than total burn surface area and burn degrees as expected. We suspect that increased supplementation of vitamin D should be based on albumin level and last until albumin levels are balanced.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1759.2-1759
Author(s):  
N. Toroptsova ◽  
O. Dobrovolskaya ◽  
O. Nikitinskaya ◽  
N. Demin ◽  
A. Smirnov ◽  
...  

Background:The onset of the disease in young and middle age is typical for rheumatic diseases (RDS), but most studies on osteoporosis were conducted in patients (pts) older than 50 years, which included postmenopausal women.Objectives:To assess bone mineral density (BMD), fracture frequency and the factors associated with low BMD in premenopausal women with RDs.Methods:160 women (median age, 36 [29; 43] years): 120 pts with RDs (43 rheumatoid arthritis (RA), 53 systemic sclerosis (SSc) and 24 psoriatic arthritis (PsA)) and 40 age-matched healthy controls were enrolled in the study. We performed a dual-energy X-ray absorptiometry (DXA, Hologic Discovery A, USA) to measure BMD in lumbar spine, femoral neck and total hip. BMD decreasing grade was evaluated by the Z-score <-2SD. All pts were interviewed using a unified questionnaire including assessment of daily dietary calcium intake. Serum vitamin D, C-reactive protein and erythrocyte sedimentation rate (ESR) measurements were done.Results:25% pts with RDs and only 8% healthy controls have low BMD (p=0.02). RA, SSc and PsA pts had low BMD in 37%, 21% and 13%, respectively, that was more often than in healthy women (p=0.004, p=0.046 and p= 0.081, respectively). 9,3% RA pts and 7,5% SSc pts had low energy fractures. BMD of RDs pts in all areas of measurement demonstrated a direct correlation with height, weight, body mass index, and serum vitamin D concentration and an inverse correlation with the cumulative dose of glucocorticoids. Also, proximal femur BMD inversely correlated with RDs duration. BMD of femoral neck and total hip inversely correlated with C-reactive protein level in SSc pts. In RA women we found a direct correlation between lumbar spine and femur neck BMD and ESR.Conclusion:25% of premenopausal women with RDs had reduced BMD and needed monitoring and osteoporosis prevention, while 9.3% pts with RA and 7.5% women with SSc needed anti-osteoporotic treatment.Disclosure of Interests:None declared


Biomarkers ◽  
2006 ◽  
Vol 11 (4) ◽  
pp. 370-382 ◽  
Author(s):  
W. K. Al-Delaimy ◽  
E. H. J. M. Jansen ◽  
P. H. M. Peeters ◽  
J. D. van der Laan ◽  
P. A. H. van Noord ◽  
...  

2021 ◽  
Vol 28 (5) ◽  
pp. 879
Author(s):  
Nalan Kozaci ◽  
Cafer Caliskan ◽  
Mustafa Avci ◽  
Gulsum Caliskan ◽  
Ilhan Uysal

2017 ◽  
Vol 47 (2) ◽  
pp. 231 ◽  
Author(s):  
Goksel Cagirci ◽  
Selcuk Kucukseymen ◽  
Isa Oner Yuksel ◽  
Nermin Bayar ◽  
Erkan Koklu ◽  
...  

2020 ◽  
Vol 77 (6) ◽  
pp. 582-589
Author(s):  
Marijana Petrovic ◽  
Tamara Dragovic ◽  
Stanko Petrovic ◽  
Katarina Obrencevic ◽  
Nemanja Rancic ◽  
...  

Background/Aim. Vitamin D insufficiency/deficiency is often present in patients with type-2 diabetes mellitus (DM) and could present a risk factor for rapid progression of diabetic nephropathy and for higher incidence of cardiovascular events. The aim of this study was to examine the influence of vitamin D supplementation on proteinuria, cholesterol, triglycerides, C-reactive protein (CRP) and hemoglobin A1c in patients with type-2 DM and vitamin D insufficiency/ deficiency. Methods. This prospective, cohort study included 90 patients with type-2 DM and vitamin D insufficiency/ deficiency divided into 3 equal groups: with normal proteinura, with microproteinuria and with macroproteinuria. Therapy included six months of supplementation with cholecalciferol drops: first two months with 20,000 IU twice weekly, than if level of vitamin D was below normal the same dose was given next four months. If the level of vitamin D was normal 5,000 IU was given twice weekly. At the begining and at the end of the study the levels of urea, creatinine, fasting blood glucose, calcium, phosphorus, cholesterol, triglycerides, CRP, hemoglobin A1c, intact parathyroid hormone, 24-hour urine protein and creatinine clearance were determined. Levels of calcium, phosphorus and vitamin D were also checked 2 months after beginning of therapy due to possible correction of cholecalciferol dose. Results. The lowest level of vitamin D before therapy was found in patients with macroproteinuria, while at the end of the study the significantly higher level of vitamin D was found in all three groups. After 6 months of therapy a significant decrease of 24-hour urine protein, cholesterol, triglycerides, hemoglobin A1c in all three groups, and CRP in patients with normal proteinuria and microproteinuria were found. Significantly negative correlation between vitamin D and 24-hour urine protein, cholesterol and CRP was found in patients with macroproteinuria. Also, significantly negative correlation was found between vitamin D and hemoglobin A1c, in patients with normal proteinuria, vitamin D and CRP in patients with microproteinuria. Conclusion. A preventive use of high-dose cholecalciferol supplementation in patients with type-2 DM (with or without proteinuria) decreases cholesterol, triglycerides, proteinuria, CRP and hemoglobin A1c.


2021 ◽  
Vol 8 (1) ◽  
pp. 21
Author(s):  
Deny Yudi Fitranti ◽  
Bunga Syifarahmi ◽  
Martha Ardiaria ◽  
Nurmasari Widyastuti

<p>Proses penuaan mempengaruhi peningkatan distribusi lemak abdominal dengan indikator lingkar pinggang (LP) dan rasio lingkar pinggang panggul (RLPP). Penimbunan lemak abdominal menyebabkan disfungsi jaringan adiposa sehingga mempengaruhi biomarker proinflamasi yaitu kadar serum <em>high-sensitivity C-reactive Protein</em> (hs-CRP). Penelitian bertujuan untuk mengetahui hubungan LP dan RLPP dengan kadar hs-CRP lansia wanita. Rancangan penelitian <em>cross sectional</em> pada 53 subjek dipilih secara <em>consecutive sampling</em>. Antropometri yang diukur adalah LP dan RLPP. Pengukuran kadar serum hs-CRP dianalisis dengan metode <em>enyme-linked immunosorbent assay</em> (ELISA). Wawancara yang dilakukan yaitu data diri, asupan, aktivitas fisik, dan riwayat konsumsi obat. Data asupan diperoleh dengan metode <em>food recall</em> 3x24 jam. Aktivitas fisik diperoleh menggunakan <em>International Physical Activity Questionnaire</em> (IPAQ). Analisis data digunakan uji korelasi <em>Spearman</em>. Hasil penelitian menunjukkan bahwa persentase LP pada lansia wanita yang berisiko sebesar 90,6%, RLPP yang berisiko sebesar 98,1%, dan kadar hs-CRP tinggi sebesar 30,2%. Terdapat hubungan positif antara LP dengan kadar serum hs-CRP (r=0,417 ; p=0,002). Dalam penelitian ini RLPP, aktivitas fisik, asupan energi, karbohidrat, protein, lemak, serat, vitamin A, vitamin C, vitamin D,vitamin E, dan selenium tidak berkorelasi dengan kadar hs-CRP. Simpulan penelitian ini adalah LP berkorelasi positif dengan kadar serum hs-CRP, namun RLPP tidak berkorelasi dengan kadar serum hs-CRP</p>


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Dan Jin ◽  
Dao-Min Zhu ◽  
Hong-Lin Hu ◽  
Meng-Nan Yao ◽  
Wan-Jun Yin ◽  
...  

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