Ueno, M. | bioRxiv Science

bioRxiv2018

Genome-wide association meta-analysis identifies novel GP2 gene risk variants for pancreatic cancer in the Japanese population

The etiology of pancreatic cancer remains largely unknown. Here, we report the results of a meta-analysis of three genome-wide association studies (GWASs) comprising 2,039 pancreatic cancer cases and 32,592 controls, the largest sample size in the Japanese population. We identified 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P<5.0x10-8) and 4 suggestive loci (P<1.0x10-6) for pancreatic cancer. Of these risk loci, 16p12.3 is novel; the lead SNP maps to rs78193826 (odds ratio (OR)=1.46, 95% CI=1.29-1.66, P=4.28x10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant predicted to be highly deleterious. Additionally, the gene-based GWAS identified a novel gene, KRT8, which is linked to exocrine pancreatic and liver diseases. The identified GP2 gene variants were pleiotropic for multiple traits, including type 2 diabetes, hemoglobin A1c (HbA1c) levels, and pancreatic cancer. Mendelian randomization analyses corroborated causality between HbA1c and pancreatic cancer. These findings suggest that GP2 gene variants are associated with pancreatic cancer susceptibility in the Japanese population, prompting further functional characterization of this locus.

genetics↗

bioRxiv2018

Characterization of oral microbiota in marmosets: feasibility of using the marmoset as a human oral disease model

As the worlds population is aging, there is an increasing demand for research regarding aging and aging-related disorders, to achieve better understanding of aging. Ideally, such research would be performed with human subjects. However, due to ethical considerations, animals such as rodents and monkeys are used as alternatives. Among these alternative models, non-human primates are preferred because they share common traits with humans. The small South American common marmoset (Callithrix jacchus) may offer a number of advantages over other non-human primates in terms of its relatively small size, short life span, and identical dental anatomy, compared with humans. The purpose of this study was to clarify the viability of using the marmoset as a human oral disease model.\n\nWe collected saliva samples from eight common marmosets and eight human subjects. Prokaryotic DNA was extracted from the saliva samples, and 16S bacterial rRNA gene sequencing was performed on each of the samples. Our results indicated that the types of oral microbiomes detected among human and marmoset samples were nearly identical. In contrast, the oral microbiomes of our human and marmoset subjects were distinctly different from those of rat and dogs, which are popular animal models. The oral microbiomes of marmosets showed greater diversity than those of humans. With respect to individual variation, marmosets exhibited less variation in their oral flora, compared with humans. This difference in variation might be attributed to the fact that marmoset subjects were kept in a controlled environment with identical lifestyles.\n\nThe characteristics of its oral microbiota, combined with other technical advantages, suggest that the marmoset may provide the best animal model thus far for the study of oral health. This study characterized the oral microbes of the marmoset, thereby providing information to support future application of the marmoset as a model for age-related oral disease.

microbiology↗