The effect of host genetics on the gut microbiome

被引：599

作者：

Bonder, Marc Jan ^{[1
]}

Kurilshikov, Alexander ^{[1
,2
,3
]}

Tigchelaar, Ettje F. ^{[1
,4
]}

Mujagic, Zlatan ^{[4
,5
]}

Imhann, Floris ^{[6
]}

Vila, Arnau Vich ^{[6
]}

Deelen, Patrick ^{[1
,7
]}

Vatanen, Tommi ^{[8
,9
]}

Schirmer, Melanie ^{[8
,10
]}

Smeekens, Sanne P. ^{[11
,12
]}

Zhernakova, Dania V. ^{[1
]}

Jankipersadsing, Soesma A. ^{[1
,13
]}

Jaeger, Martin ^{[11
,12
]}

Oosting, Marije ^{[11
,12
]}

Cenit, Maria Carmen ^{[1
,18
]}

Masclee, Ad A. M. ^{[5
]}

Swertz, Morris A. ^{[1
,7
]}

Li, Yang ^{[1
]}

Kumar, Vinod ^{[1
]}

Joosten, Leo ^{[11
,12
]}

Harmsen, Hermie ^{[14
]}

Weersma, Rinse K. ^{[6
]}

Franke, Lude ^{[1
]}

Hofker, Marten H. ^{[13
]}

Xavier, Ramnik J. ^{[8
,15
,16
,17
]}

Jonkers, Daisy ^{[5
]}

Netea, Mihai G. ^{[11
,12
]}

Wijmenga, Cisca ^{[1
]}

Fu, Jingyuan ^{[1
,13
]}

Zhernakova, Alexandra ^{[1
,4
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[2] RAS, Inst Chem Biol & Fundamental Med, SB, Novosibirsk, Russia

[3] Novosibirsk State Univ, Dept Nat Sci, Novosibirsk, Russia

[4] Top Inst Food & Nutr, Wageningen, Netherlands

[5] Maastricht Univ, NUTRIM Sch Nutr & Translat Res Metab, Div Gastroenterol Hepatol, Dept Internal Med Med Ctr, Maastricht, Netherlands

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands

[7] Univ Groningen, Univ Med Ctr Groningen, Genom Coordinat Ctr, Groningen, Netherlands

[8] Broad Inst MIT & Harvard, Cambridge, MA USA

[9] Aalto Univ, Dept Comp Sci, Sch Sci, Espoo, Finland

[10] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[11] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands

[12] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands

[13] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat, Groningen, Netherlands

[14] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol, Groningen, Netherlands

[15] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[16] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[17] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[18] Dr Peset Univ Hosp, Dept Pediat, Valencia, Spain

来源：

NATURE GENETICS | 2016年 / 48卷 / 11期

基金：

欧洲研究理事会;

关键词：

INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; LACTASE PERSISTENCE; COLORECTAL-CANCER; RECEPTOR; EXPRESSION; DIVERSITY; VARIANTS; OBESITY;

D O I：

10.1038/ng.3663

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The gut microbiome is affected by multiple factors, including genetics. In this study, we assessed the influence of host genetics on microbial species, pathways and gene ontology categories, on the basis of metagenomic sequencing in 1,514 subjects. In a genome-wide analysis, we identified associations of 9 loci with microbial taxonomies and 33 loci with microbial pathways and gene ontology terms at P < 5 x 10(-8). Additionally, in a targeted analysis of regions involved in complex diseases, innate and adaptive immunity, or food preferences, 32 loci were identified at the suggestive level of P < 5 x 10(-6). Most of our reported associations are new, including genome-wide significance for the C-type lectin molecules CLEC4F-CD207 at 2p13.3 and CLEC4A-FAM90A1 at 12p13. We also identified association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 x 10(-8)) and provide evidence of a gene-diet interaction in the regulation of Bifidobacterium abundance. Our, results demonstrate the importance of understanding host-microbe interactions to gain better insight into human health.

引用

页码：1407 / 1412

页数：6

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