학술논문

Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort
Document Type
article
Source
Nature Genetics. 54(2)
Subject
Microbiology
Biological Sciences
Genetics
Prevention
Digestive Diseases
Nutrition
Human Genome
Clinical Research
Aetiology
2.1 Biological and endogenous factors
Oral and gastrointestinal
ABO Blood-Group System
Bifidobacterium
Clostridiales
Cohort Studies
Colorectal Neoplasms
Depressive Disorder
Major
Diet
Dietary Fiber
Enterococcus faecalis
Gastrointestinal Microbiome
Gastrointestinal Tract
Genetic Variation
Genome-Wide Association Study
Host Microbial Interactions
Humans
Lactase
Mediator Complex
Mendelian Randomization Analysis
Metagenome
Morganella
Polymorphism
Single Nucleotide
Medical and Health Sciences
Developmental Biology
Agricultural biotechnology
Bioinformatics and computational biology
Language
Abstract
Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.