Large-scale association analyses identify host factors influencing human gut microbiome composition

被引：1199

作者：

Kurilshikov, Alexander ^{[1
]}

Medina-Gomez, Carolina ^{[2
,3
]}

Bacigalupe, Rodrigo ^{[4
,5
]}

Radjabzadeh, Djawad ^{[2
]}

Wang, Jun ^{[4
,5
,6
]}

Demirkan, Ayse ^{[1
,7
]}

Le Roy, Caroline, I ^{[8
]}

Garay, Juan Antonio Raygoza ^{[9
,10
]}

Finnicum, Casey T. ^{[11
,12
]}

Liu, Xingrong ^{[13
,14
]}

Zhernakova, Daria, V ^{[1
,15
]}

Bonder, Marc Jan ^{[1
]}

Hansen, Tue H. ^{[16
]}

Frost, Fabian ^{[17
]}

Ruhlemann, Malte C. ^{[18
]}

Turpin, Williams ^{[9
,10
]}

Moon, Jee-Young ^{[19
]}

Kim, Han-Na ^{[20
,21
]}

Lull, Kreete ^{[22
]}

Barkan, Elad ^{[23
]}

Shah, Shiraz A. ^{[24
]}

Fornage, Myriam ^{[25
]}

Szopinska-Tokov, Joanna ^{[26
,27
]}

Wallen, Zachary D. ^{[28
]}

Borisevich, Dmitrii ^{[16
]}

Agreus, Lars ^{[29
]}

Andreasson, Anna ^{[30
]}

Bang, Corinna ^{[18
]}

Bedrani, Larbi ^{[9
]}

Bell, Jordana T. ^{[8
]}

Bisgaard, Hans ^{[24
]}

Boehnke, Michael ^{[31
,32
]}

Boomsma, Dorret, I ^{[33
]}

Burk, Robert D. ^{[34
,35
]}

Claringbould, Annique ^{[1
]}

Croitoru, Kenneth ^{[9
,10
]}

Davies, Gareth E. ^{[11
,12
,33
]}

van Duijn, Cornelia M. ^{[36
,37
]}

Duijts, Liesbeth ^{[3
,38
]}

Falony, Gwen ^{[4
,5
]}

Fu, Jingyuan ^{[1
,39
]}

van der Graaf, Adriaan ^{[1
]}

Hansen, Torben ^{[16
]}

Homuth, Georg ^{[40
]}

Hughes, David A. ^{[41
,42
]}

Ijzerman, Richard G. ^{[43
]}

Jackson, Matthew A. ^{[8
,44
]}

Jaddoe, Vincent W. V. ^{[3
,36
]}

Joossens, Marie ^{[4
,5
]}

Jorgensen, Torben ^{[45
,46
]}

机构：

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

[2] Erasmus MC Univ Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[3] Erasmus MC Univ Med Ctr, Generat R Study, Rotterdam, Netherlands

[4] Katholieke Univ Leuven, Dept Microbiol & Immunol, Rega Inst, Leuven, Belgium

[5] VIB, Ctr Microbiol, Leuven, Belgium

[6] Chinese Acad Sci, Inst Microbiol, Beijing, Peoples R China

[7] Univ Surrey, Sch Biosci & Med, Dept Clin & Expt Med, Sect Stat Multiomics, Guildford, Surrey, England

[8] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[9] Univ Toronto, Dept Med, Toronto, ON, Canada

[10] Mt Sinai Hosp, Div Gastroenterol, Toronto, ON, Canada

[11] Avera McKennan Hosp, Avera Inst Human Genet, Sioux Falls, SD USA

[12] Univ Hlth Ctr, Sioux Falls, SD USA

[13] Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden

[14] Karolinska Inst, Dept Med Solna, Clin Epidemiol Div, Stockholm, Sweden

[15] ITMO Univ, Ctr Comp Technol, Lab Genom Divers, St Petersburg, Russia

[16] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark

[17] Univ Med Greifswald, Dept Med A, Greifswald, Germany

[18] Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[19] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA

[20] Sungkyunkwan Univ, Kangbuk Samsung Hosp, Med Res Inst, Sch Med, Seoul, South Korea

[21] Sungkyunkwan Univ, Dept Clin Res Design & Evaluat, SAIHST, Seoul, South Korea

[22] Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia

[23] Weizmann Inst Sci, Dept Comp Sci & Cell Biol, Rehovot, Israel

[24] Copenhagen Univ Hosp, COPSAC, Copenhagen, Denmark

[25] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med McGovern Med Sch, Houston, TX 77030 USA

[26] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr Sch Publ Hlth, Houston, TX USA

[27] Radboudumc, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[28] Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA

[29] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden

[30] Stockholm Univ, Stress Res Inst, Stockholm, Sweden

[31] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[32] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[33] Vrije Univ, Biol Psychol, Amsterdam, Netherlands

[34] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA

[35] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA

[36] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[37] Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England

[38] Erasmus MC Univ Med Ctr, Dept Pediat, Rotterdam, Netherlands

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

[40] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany

[41] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[42] Univ Bristol Sch Med, Populat Hlth Sci, Bristol, Avon, England

[43] Amsterdam Univ Med Ctr, Dept Endocrinol, Locat VUMC, Amsterdam, Netherlands

[44] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England

[45] Univ Copenhagen, Bispebjerg Frederiksberg Hosp, Capital Reg Copenhagen, Ctr Clin Res & Prevent, Copenhagen, Denmark

[46] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[47] Maastricht Univ Med Ctr, Div Gastroenterol Hepatol, Maastricht, Netherlands

[48] Maastricht Univ, NUTRIM Sch Nutr & Translat Res Metab, Maastricht, Netherlands

[49] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[50] Univ Calif San Diego, Ctr Microbiome Innovat, La Jolla, CA 92093 USA

来源：

NATURE GENETICS | 2021年 / 53卷 / 02期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; MENDELIAN RANDOMIZATION; GENOTYPE IMPUTATION; GENETICS; IDENTIFICATION; ENVIRONMENT; METAGENOME; FRAMEWORK; ECOSYSTEM; DISEASES;

D O I：

10.1038/s41588-020-00763-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：156 / +

页数：19

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