作者: Laeya Abdoli Najmi , Ingvild Aukrust , Jason Flannick , Janne Molnes , Noel Burtt
DOI: 10.2337/DB16-0460
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摘要: Variants in HNF1A encoding hepatocyte nuclear factor 1α (HNF-1A) are associated with maturity-onset diabetes of the young form 3 (MODY 3) and type 2 diabetes. We investigated whether functional classification rare coding variants can inform models risk prediction general population by analyzing effect 27 identified well-phenotyped populations (n = 4,115). Bioinformatics tools classified 11 as likely pathogenic showed no association (combined minor allele frequency [MAF] 0.22%; odds ratio [OR] 2.02; 95% CI 0.73-5.60; P 0.18). However, a different set that reduced HNF-1A transcriptional activity to <60% normal (wild-type) was strongly MAF OR 5.04; 1.99-12.80; 0.0007). Our investigations indicate 0.44% carry result substantially increased for developing These results suggest characterization within MODY genes may overcome limitations bioinformatics purposes presymptomatic population.