The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young otherwise healthy individuals. We conducted genome-wide association studies (GWAS) and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases), and nine left ventricular (LV) traits in 19,260 UK Biobank participants with structurally normal hearts. We identified 16 loci associated with HCM, 13 with DCM, and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased contractility with HCM risk. A polygenic risk score (PRS) explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that PRS may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.

PROSPERO CRD42017069390.

Accessible summary What is known on the subject? Aggressive behaviour is a major problem in clinical practice of mental health care and can result in the use of coercive measures. Coercive measures are dangerous for psychiatric patients and international mental healthcare works on the elimination of these interventions. There is no previous review that summarizes the attitude of nursing staff towards coercive measures and the influence of nursing staff characteristics on attitude towards and the use of coercive measures. What the paper adds to existing knowledge? The attitude of nurses shifted from a therapeutic paradigm (coercive measures have positive effects on patients) to a safety paradigm (coercive measures are undesirable, but necessary for the wards’ safety). Nurses express the need for less coercive interventions to prevent seclusion and restraint, but their perception of intrusiveness is influenced by how often they use specific coercive measures. The knowledge from scientific literature on the influence of nursing staff on coercive measures is highly inconclusive, although the feeling of safety of nurses might prove to be promising for further research. What are the implications for practice? There is need for increased attention specifically for the feeling of safety of nurses, to better equip nurses for their difficult work on acute mental health wards. Abstract Introduction The use of coercive measures generally has negative effects on patients. To help prevent its use, professionals need insight into what nurses believe about coercion and which staff determinants may influence its application. There is need for an integrated review on both attitude and influence of nurses on the use of coercion. Aim To summarize literature concerning attitude of nurses towards coercive measures and the influence of staff characteristics on the use of coercive measures. Method Systematic review. Results The attitude of nurses changed during the last two decades from a therapeutic to a safety paradigm. Nurses currently view coercive measures as undesirable, but necessary to deal with aggression. Nurses express the need for less intrusive interventions, although familiarity probably influences its perceived intrusiveness. Literature on the relation between staff characteristics and coercive measures is inconclusive. Discussion Nurses perceive coercive measures as unwanted but still necessary to maintain safety on psychiatric wards. Focussing on the determinants of perception of safety might be a promising direction for future research. Implications for practice Mental health care could improve the focus on the co...