BackgroundFace morphology is strongly determined by genetic factors. However, only a small number of genes related to face morphology have been identified to date. Here, we performed a two-stage genome-wide association study (GWAS) of 85 face morphological traits in 7569 Koreans (5643 in the discovery set and 1926 in the replication set).ResultsIn this study, we analyzed 85 facial traits, including facial angles. After discovery GWAS, 128 single nucleotide polymorphisms (SNPs) showing an association of P < 5 × 10− 6 were selected to determine the replication of the associations, and meta-analysis of discovery GWAS and the replication analysis resulted in five genome-wide significant loci. The OSR1-WDR35 [rs7567283, G allele, beta (se) = −0.536 (0.096), P = 2.75 × 10− 8] locus was associated with the facial frontal contour; the HOXD1-MTX2 [rs970797, A allele, beta (se) = 0.015 (0.003), P = 3.97 × 10− 9] and WDR27 [rs3736712, C allele, beta (se) = 0.293 (0.048), P = 8.44 × 10− 10] loci were associated with eye shape; and the SOX9 [rs2193054, C allele, beta (se) (ln-transformed) = −0.007 (0.001), P = 6.17 × 10− 17] and DHX35 [rs2206437, A allele, beta (se) = −0.283 (0.047), P = 1.61 × 10− 9] loci were associated with nose shape. WDR35 and SOX9 were related to known craniofacial malformations, i.e., cranioectodermal dysplasia 2 and campomelic dysplasia, respectively. In addition, we found three independent association signals in the SOX9 locus, and six known loci for nose size and shape were replicated in this study population. Interestingly, four SNPs within these five face morphology-related loci showed discrepancies in allele frequencies among ethnic groups.ConclusionsWe identified five novel face morphology loci that were associated with facial frontal contour, nose shape, and eye shape. Our findings provide useful genetic information for the determination of face morphology.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4865-9) contains supplementary material, which is available to authorized users.

The link between brain amyloid-β (Aβ), metabolism, and dementia symptoms remains a pressing question in Alzheimer’s disease. Here, using positron emission tomography ([ 18 F]florbetapir tracer for Aβ and [ 18 F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aβ aggregation within the brain’s default mode network leads to regional hypometabolism in distant but functionally connected brain regions. Moreover, we found that an interaction between this hypometabolism with overlapping Aβ aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aβ rats that do not form neurofibrillary tangles, which support these findings as an independent mechanism of cognitive deterioration. These results suggest a model in which distant Aβ induces regional metabolic vulnerability, whereas the interaction between local Aβ with a vulnerable environment drives the clinical progression of dementia.

Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia, atherosclerosis, hypertension, dysentery, inflammatory diseases, and the common cold. The present study was performed to investigate the anti-obesity and anti-dyslipidemia effect of Scutellaria baicalensis extracts (SBE) in type 2 diabetic db/db mice. Male db/db mice were divided into three groups (n = 5) and orally administrated vehicle (control), SBE 10, and 100 mg/kg body weight/day for 4 weeks everyday. Administration of SBE improves weight gain, hypertriglyceridemia, and hyperinsulinemia in db/db mice. In obese db/db mice, SBE treatment also reduced plasma alanine aminotransferase levels. In the livers of db/db mice, SBE promoted 5' AMP-activated protein kinase activity and restored metabolic process and insulin signaling pathways. Our data demonstrate that SBE exerts potent anti-obesity and anti-hypertriglyceride effects suggesting its useful potential function as adjuvant therapeutic agent for the treatment of weight gain and hypertriglyceridemia.

PurposeWe aimed to determine the amyloid (Aβ) and tau biomarker levels associated with imminent Alzheimer’s disease (AD) - related metabolic decline in cognitively normal individuals.MethodsA threshold analysis was performed in 120 cognitively normal elderly individuals by modelling 2-year declines in brain glucose metabolism measured with [18F]fluorodeoxyglucose ([18F]FDG) as a function of [18F]florbetapir Aβ positron emission tomography (PET) and cerebrospinal fluid phosphorylated tau biomarker thresholds. Additionally, using a novel voxel-wise analytical framework, we determined the sample sizes needed to test an estimated 25% drugeffect with 80% of power on changes in FDG uptake over 2 years at every brain voxel.ResultsThe combination of [18F]florbetapir standardized uptake value ratios and phosphorylated-tau levels more than one standard deviation higher than their respective thresholds for biomarker abnormality was the best predictor of metabolic decline in individuals with preclinical AD. We also found that a clinical trial using these thresholds would require as few as 100 individuals to test a 25% drug effect on AD-related metabolic decline over 2 years.ConclusionsThese results highlight the new concept that combined Aβ and tau thresholds can predict imminent neurodegeneration as an alternative framework with a high statistical power for testing the effect of disease-modifying therapies on [18F]FDG uptake decline over a typical 2-year clinical trial period in individuals with preclinical AD.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-3933-3) contains supplementary material, which is available to authorized users.

BackgroundIn adipose tissues, adipokine levels, including adiponectin and leptin, are involved in insulin sensitivity and are reciprocally induced by cold temperature stress. Thermogenic response in the extremities (hands and feet) against cold stress can be negatively related to fat mass accumulation, particularly in the abdomen. However, the relationship between the sensation of cold in the extremities and circulating levels of adipokines is not fully understood. Here, we investigated whether adipokine levels are associated with cold hypersensitivity in the hands and feet (CHHF), independent of body mass, and whether the CHHF is related to metabolic syndrome (MS).MethodsAssociations of the CHHF with serum levels of adipokines and MS risk were evaluated in 1021 Koreans (372 men and 649 women), using a linear regression model while controlling for thermogenic factors and a logistic regression model, respectively.ResultsThe adiponectin levels were positively associated with the CHHF, particularly in women, irrespective of thermogenic factors, including body mass index (β = 1.23 μg/mL, 95% confidence interval [1.04–1.45]). Logistic regression analysis for MS risk via the CHHF showed that there was a significant inverse association in women (odds ratio = 0.449, 95% confidence interval [0.273–0.737]).ConclusionsIn summary, our founding indicated that the CHHF could induce increased levels of circulating adiponectin and in turn reduce the MS risk in women. Despite complaints of feeling cold, these women could be at lower risk of cardiovascular disease.