SignificanceAlzheimer’s disease (AD) is an age-related neurodegenerative disease. Genome-wide association studies predominately focusing on Caucasian populations have identified risk loci and genes associated with AD; the majority of these variants reside in noncoding regions with unclear functions. Here, we report a whole-genome sequencing study for AD in the Chinese population. Other than the APOE locus, we identified common variants in GCH1 and KCNJ15 that show suggestive associations with AD. For these two risk variants, an association with AD or advanced onset of disease can be observed in non-Asian AD cohorts. An association study of risk variants with expression data revealed their modulatory effects on immune signatures, linking the potential roles of these genes with immune-related pathways during AD pathogenesis.

Chronic stress and over-activity in the hypothalamic-pituitary-adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it's normally decreasing. To extend these findings to humans, we hypothesized that habitual breakfast skippers would display a similar pattern of circulating cortisol and alterations in meal and stress-induced cortisol reactions. Normal weight to obese women aged 18-45 years old who were strictly defined as either breakfast skippers (n=30) or breakfast eaters (n=35) were invited to participate in our study. Normal breakfast habits were maintained for the entire study period and each participant attended 4 lab visits. Over the first 2 lab visits, body composition, fasting clinical chemistries, and self-reports of chronic stress were assessed. On each of 2 additional days (lab visits 3 and 4), salivary free cortisol was measured at home upon waking and at bedtime, and in the lab in response to a standard lunch, ad libitum afternoon snack buffet, and stress and control (relaxation) tasks. The order of the control and stress test visits was randomized. While body weight, body composition, HOMA-IR, total and HDL cholesterol did not statistically differ (p>0.05), both diastolic and systolic blood pressure was elevated (p<0.01) and LDL cholesterol was lower (p=0.04) in the breakfast skipper group. Compared to the breakfast eaters and on the control task visit only, breakfast skippers had higher circulating cortisol from arrival to midafternoon (p<0.01) and during the snack buffet (p<0.05). Furthermore, the lunch-induced cortisol reaction was larger in the 'skippers' (p=0.03). On both stress and control visit days, the diurnal cortisol amplitude was significantly (p=0.02) blunted in breakfast skippers. Self-reports of chronic stress did not differ between the groups. These data indicate that habitually skipping breakfast is associated with stress-independent over-activity in the HPA axis which, if prolonged, may increase risk (e.g., hypertension) for cardiometabolic disease in some people.

Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD) or ≤4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT), subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered.

The consumption of a DGA dietary pattern for 8 wk without weight loss reduced systolic blood pressure. There were no differences between the DGA and TAD diets in fasting insulin, glucose, indexes of insulin resistance, or fasting lipids. This trial was registered at www.clinicaltrials.gov as NCT02298725.