Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Identifying important outcomes for young people with chronic kidney disease and their caregivers: a nominal group technique study

RATIONALE AND OBJECTIVE: Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision-making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers. STUDY DESIGN: We used the nominal group technique whereby participants identified and ranked outcomes and explained their priorities. SETTING AND PARTICIPANTS: Young people with CKD (stage 1-5, dialysis or transplant) and their caregivers were purposively sampled from six centers across Australia, the United States and Canada. ANALYTICAL APPROACH: Importance scores were calculated (scale of 0 to 1), and qualitative data were analyzed thematically. Results: Thirty-four patients (aged 8-21 years) and 62 caregivers participated in 16 groups, and identified 48 outcomes. The five highest ranked outcomes for patients were survival (importance score = 0.25), physical activity (0.24), fatigue (0.20), lifestyle restrictions (0.20) and growth (0.20), and for caregivers, kidney function (0.53), survival (0.28), infection (0.22), anemia (0.20) and growth (0.17). Twelve themes were identified reflecting their immediate and current priorities (wanting to feel normal, strengthening resilience, minimizing intrusion into daily life, imminent threats to life, devastating family burdens, and seeking control over health) and considerations regarding future impacts (protecting health/development, remaining hopeful, concern for limited opportunities, prognostic uncertainty, dreading painful and invasive procedures and managing expectations). LIMITATIONS: Only English-speaking participants were recruited. CONCLUSIONS: Kidney function, infection, survival and growth were the highest priorities for patients with CKD and their caregivers. Young people with CKD also prioritized highly the outcomes that directly affected their lifestyle and sense of normality, while caregiver’s highest priorities concerned the long-term health of their child, current health problems, and the financial and family burdens of caring for a child with CKD