Genetic variation in HTR4 and lung function: GWAS follow-up in mouse

摘要: Human genome-wide association studies (GWASs) have identified numerous associations between single nucleotide polymorphisms (SNPs) and pulmonary function. Proving that there is a causal relationship GWAS SNPs, many of which are noncoding without known functional impact, these traits has been elusive. Furthermore, GWAS-identified SNPs may exert trans-regulatory effects rather than impact the proximal gene. Noncoding variants in 5-hydroxytryptamine (serotonin) receptor 4 (HTR4) associated with function human GWASs. To gain insight into whether this causal, we tested Htr4-null mice altered We found HTR4-deficient 12% higher baseline lung resistance also increased methacholine-induced airway hyperresponsiveness (AHR) as measured by (27%), tissue (48%), elastance (30%). were more sensitive to serotonin-induced AHR. In models exposure ...