INTRODUCTION: The family history of inflammatory bowel disease (IBD) has been strongly associated with risk of developing IBD. This study aimed to identify the host genetic and gut microbial signatures in familial IBD. METHODS: Genetic analyses using genome-wide single nucleotide polymorphism genotyping and whole exome sequencing were performed to calculate weighted genetic risk scores from known IBD-associated common variants and to identify rare deleterious protein-altering variants specific to patients with familial IBD in 8 Korean families that each included more than 2 affected first-degree relatives (FDRs) and their unaffected FDR(s). In parallel, gut microbial community was analyzed by 16S rRNA sequencing of stools from the sample individuals. RESULTS: The risk of familial IBD was not well explained by the genetic burden from common IBD-risk variants, suggesting the presence of family-shared genetic and environmental disease-risk factors. We identified 17 genes ( AC113554.1 , ACE , AKAP17A , AKAP9 , ANK2 , ASB16 , ASIC3 , DNPH1 , DUS3L , FAM200A , FZD10 , LAMA5 , NUTM2F , PKN1 , PRR26 , WDR66 , and ZC3H4 ) that each contained rare, potentially deleterious variants transmitted to the affected FDRs in multiple families. In addition, metagenomic analyses revealed significantly different diversity of gut microbiota and identified a number of differentially abundant taxa in affected FDRs, highlighting 22 novel familial disease-associated taxa with large abundance changes and the previously reported gut dysbiosis including low alpha diversity in IBD and 16 known IBD-specific taxa. DISCUSSION: This study identified familial IBD-associated rare deleterious variants and gut microbial dysbiosis in familial IBD.
Background Skin assessment methodologies have focused mainly on intuitive aging characteristics, including facial wrinkles and pigmented spots, and usually adopt pattern recognition algorithms. Recently, distinct methods of interpreting skin aging, such as the detection of facial landmarks and age prediction using machine learning techniques, have been conducted. Materials and Methods We defined two indices that represent the severity of facial aging. The first index was the ratio of the bizygomatic distance and bigonial distance. The second index was the ratio of the degrees of the near mandible. The indices extracted from two‐dimensional frontal face images were intended to show the deformation of the facial skin downward with aging progress. To validate whether these proposed indicators can represent facial aging, we conducted correlation tests with age and facial skin characteristics and performed association tests between the indices and facial skin characteristics, adjusted for age. Results The indices showed strong correlations with age (r = 0.557 and 0.464, respectively) and facial skin characteristics. Although there were correlations between the indices and facial skin features, the associations between the indices and facial skin characteristics adjusted for age were weak or not significant. This suggests that the newly developed indices are appropriate for evaluating facial skin aging and distinct from typical measurements. Conclusion We suggest two novel indices for evaluating facial aging based on frontal face images. The indices exhibited strong correlations with age and representative facial skin characteristics. The newly developed values can be differentiated indicators of facial aging compared with general skin features.
Background Familial IBD may have its own signatures with respect to host genetic variants and/or gut microbiome. However, available data focussing on this topic is still limited, particularly for Asian patients with familial IBD. We aimed to investigate the possible host genetic and gut microbial signatures in familial IBD through a combined analysis of genomic and metagenomic profiles. Methods All patients were affiliated with a prospectively recruited cohort of patients with IBD (NCT03589183) and met the diagnostic criteria of Crohn’s disease (CD) or ulcerative colitis (UC). We constructed a unique family cohort comprising ≥2 affected individuals with familial IBD and ≥1 their unaffected, healthy first-degree relative (FDR) in each family. Whole-exome sequencing for rare variants followed by a genome-wide single-nucleotide polymorphism analysis for common variants was performed. A polygenic risk score (PRS) was calculated separately in Crohn’s disease (CD), ulcerative colitis (UC) or IBD. Gut microbial community was analysed by 16s rRNA sequencing of stool samples. Results Eight Korean families comprising 16 with familial IBD (12 concordant IBD, 4 discordant IBD) and 9 FDRs were included for analysis. Whole-exome sequencing identified four family-specific candidate genes (LAMA5, MYO15B, TTN, and WDR66) with rare missense variants that were transmitted preferentially to the affected FDRs in at least ≥3 families (Figure 1). An in silico analysis identified the deleterious effect of the identified variants on the gene products including LAMA5 (SIFT = 0, PolyPhen-2 = 0.72). The patients with CD, but not those with UC, had a significantly higher mean PRS than controls (PRS = 2.137 vs. 0.742, p-value = 0.030). Metagenomic sequencing revealed significant differences in α- and β-diversity of gut microbiota among the patients with CD, those with UC, and unaffected FDRs (all p < 0.05), showing lower microbial richness in the patients with familial IBD (p = 0.02). In various taxonomic levels, compared with unaffected FDRs, the patients with familial IBD showed the significantly differential abundance of several gut bacteria (all corrected p < 0.05; Figure 2). Conclusion Family-specific host genetic and gut microbial signatures have a beneficial role in early-identification of familial IBD (NCT03515070).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.