A Genome-Wide Association Study of the Protein C Anticoagulant Pathway

The Protein C anticoagulant pathway regulates blood coagulation by preventing the inadequate formation of thrombi. It has two main plasma components: protein C and protein S. Individuals with protein C or protein S deficiency present a dramatically increased incidence of thromboembolic disorders. Here, we present the results of a genome-wide association study (GWAS) for protein C and protein S plasma levels in a set of extended pedigrees from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. A total number of 397 individuals from 21 families were typed for 307,984 SNPs using the Infinium® 317 k Beadchip (Illumina). Protein C and protein S (free, functional and total) plasma levels were determined with biochemical assays for all participants. Association with phenotypes was investigated through variance component analysis. After correcting for multiple testing, two SNPs for protein C plasma levels (rs867186 and rs8119351) and another two for free protein S plasma levels (rs1413885 and rs1570868) remained significant on a genome-wide level, located in and around the PROCR and the DNAJC6 genomic regions respectively. No SNPs were significantly associated with functional or total protein S plasma levels, although rs1413885 from DNAJC6 showed suggestive association with the functional protein S phenotype, possibly indicating that this locus plays an important role in protein S metabolism. Our results provide evidence that PROCR and DNAJC6 might play a role in protein C and free protein S plasma levels in the population studied, warranting further investigation on the role of these loci in the etiology of venous thromboembolism and other thrombotic diseases

Testing an mHealth Momentary Assessment Routine Outcome Monitoring Application: A Focus on Restoration of Daily Life Positive Mood States

Routine Outcome Monitoring (ROM) is used as a means to enrich the process of treatment with feedback on patient outcomes, facilitating patient involvement and shared decision making. While traditional ROM measures focus on retrospective accounts of symptoms, novel mHealth technology makes it possible to collect real life, in-the-moment ambulatory data that allow for an ecologically valid assessment of personalized and contextualized emotional and behavioural adjustment in the flow daily life (mROM).In a sample of 34 patients with major depressive disorder, treated with antidepressants, the combined effect of treatment and natural course was examined over a period of 18 weeks with Ecological Momentary Assessment (EMA). EMA consisted of repeated, within-subject, mini-measurements of experience (eg positive affect, negative affect, medication side effects) and context (eg stressors, situations, activities) at 10 unselected semi-random moments per day, for a period of six days, repeated three times over the 18-week period (baseline, week 6 and week 18).EMA measures of emotional and behavioural adjustment were sensitive to the effects of treatment and natural course over the 18-week period, particularly EMA measures focussing on positive mood states and the ability to use natural rewards (impact of positive events on positive mood states), with standardized effect sizes of 0.4-0.5. EMA measures of activities, social interaction, stress-sensitivity and negative mood states were also sensitive to change over time.This study supports the use of mROM as a means to involve the patient in the process of needs assessment and treatment. EMA data are meaningful to the patient, as they reflect daily life circumstances. Assessment of treatment response with mROM data allows for an interpretation of the effect of treatment at the level of daily life emotional and social adjustment--as an index of health, obviating the need for an exclusive focus on traditional measures of 'sickness'