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Large-scale association analyses identify host factors influencing human gut microbiome composition
Univ Groningen, Netherlands.
Erasmus MC Univ Med Ctr, Netherlands; Erasmus MC Univ Med Ctr, Netherlands.
Katholieke Univ Leuven, Belgium; VIB, Belgium.
Erasmus MC Univ Med Ctr, Netherlands.
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2021 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 53, no 2, p. 156-165Article in journal (Refereed) Published
Abstract [en]

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Place, publisher, year, edition, pages
Nature Publishing Group, 2021. Vol. 53, no 2, p. 156-165
National Category
Genetics
Identifiers
URN: urn:nbn:se:liu:diva-174837DOI: 10.1038/s41588-020-00763-1ISI: 000608658900003PubMedID: 33462485Scopus ID: 2-s2.0-85100210047OAI: oai:DiVA.org:liu-174837DiVA, id: diva2:1542273
Note

Funding Agencies|Cancer Research UKCancer Research UK [C18281/A19169] Funding Source: Medline; CIHRCanadian Institutes of Health Research (CIHR) [CMF108031] Funding Source: Medline; Department of HealthEuropean Commission [BRC-1215-20011] Funding Source: Medline; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MR/N01183X/1, MC_UU_12013/3, MC_UU_00011/6] Funding Source: Medline; NCATS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1 TR002489] Funding Source: Medline; NHGRI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [U01 HG004729, U01 HG004446] Funding Source: Medline; NHLBI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01 HL140976, N01HC65236, N01HC65234, N01HC65237, N01HC65226, N01HC65235, HHSN268201300005C, N01HC65233] Funding Source: Medline; NIDDK NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01 DK062370, P30 DK056350, R01 DK092127] Funding Source: Medline; NIMHD NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Minority Health & Health Disparities (NIMHD) [R01 MD011389] Funding Source: Medline; NIMH NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [U24 MH068457, RC2 MH089951, RC2 MH089995] Funding Source: Medline; NINDS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [T32 NS095775] Funding Source: Medline; Wellcome TrustWellcome TrustEuropean Commission [202802/Z/16/Z, 204813/Z/16/Z] Funding Source: Medline

Available from: 2021-04-07 Created: 2021-04-07 Last updated: 2024-01-10Bibliographically approved

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Division of Inflammation and InfectionFaculty of Medicine and Health SciencesMag- tarmmedicinska kliniken
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