Interaction between filaggrin mutations and neonatal cat exposure in atopic dermatitis
Atopic dermatitis (AD) is a prevalent inflammatory skin disease. Loss-of-function mutations in filaggrin gene (FLG) represent the strongest genetic risk factors for AD, being strongly associated with early disease onset and persistence into adulthood.1 The epidermis of individuals with mutations in FLG is fundamentally different from normal skin being characterized by increased penetration of allergens.2 Recent birth cohort studies showed a significant interaction between cat ownership at birth and mutations in FLG (R501X, 2282del4) on the development of early-onset AD.3 This finding was replicated for the 2282del4 FLG mutation in a Dutch cohort study, and extended to further associate with…
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 d…
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function
Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may p…
Acute Laryngitis in the Rat Induced by Moraxella catarrhalis and Bordetella pertussis: Number of Neutrophils, Dendritic Cells, and T and B Lymphocytes Accumulating during Infection in the Laryngeal Mucosa Strongly Differs in Adjacent Locations
Infectious laryngotracheitis results in fulminant respiratory distress. During the disease, the subglottic mucosa is selectively infected and swollen, the reason for this preference being unknown. Therefore, in the present study the immunoreaction of the laryngeal mucosa was studied in the rat after inhalation of either heat-killed Moraxella catarrhalis (PVG rats) or application of viable Bordetella pertussis (BN rats). The number of neutrophils, macrophages, dendritic cells, and T and B lymphocytes was determined in the mucosa of the supraglottic, glottic, and subglottic area of the larynx as well as in the trachea. After application of the pathogens, the mucosa of the subglottic area was …