Large-scale association analyses identify host factors influencing human gut microbiome composition.
Large-scale association analyses identify host factors influencing human gut microbiome composition.
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大规模关联分析确定了影响人类肠道微生物组组成的宿主因素
DOI：
10.1038/s41588-020-00763-1
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发表时间：
2021-03
期刊：
影响因子：
30.8
通讯作者：
Zhernakova A
中科院分区：
文献类型：
--
作者：
Kurilshikov A;Medina-Gomez C;Bacigalupe R;Radjabzadeh D;Wang J;Demirkan A;Le Roy CI;Raygoza Garay JA;Finnicum CT;Liu X;Zhernakova DV;Bonder MJ;Hansen TH;Frost F;Rühlemann MC;Turpin W;Moon JY;Kim HN;Lüll K;Barkan E;Shah SA;Fornage M;Szopinska-Tokov J;Wallen ZD;Borisevich D;Agreus L;Andreasson A;Bang C;Bedrani L;Bell JT;Bisgaard H;Boehnke M;Boomsma DI;Burk RD;Claringbould A;Croitoru K;Davies GE;van Duijn CM;Duijts L;Falony G;Fu J;van der Graaf A;Hansen T;Homuth G;Hughes DA;Ijzerman RG;Jackson MA;Jaddoe VWV;Joossens M;Jørgensen T;Keszthelyi D;Knight R;Laakso M;Laudes M;Launer LJ;Lieb W;Lusis AJ;Masclee AAM;Moll HA;Mujagic Z;Qibin Q;Rothschild D;Shin H;Sørensen SJ;Steves CJ;Thorsen J;Timpson NJ;Tito RY;Vieira-Silva S;Völker U;Völzke H;Võsa U;Wade KH;Walter S;Watanabe K;Weiss S;Weiss FU;Weissbrod O;Westra HJ;Willemsen G;Payami H;Jonkers DMAE;Arias Vasquez A;de Geus EJC;Meyer KA;Stokholm J;Segal E;Org E;Wijmenga C;Kim HL;Kaplan RC;Spector TD;Uitterlinden AG;Rivadeneira F;Franke A;Lerch MM;Franke L;Sanna S;D'Amato M;Pedersen O;Paterson AD;Kraaij R;Raes J;Zhernakova A
为了研究宿主遗传对肠道微生物组组成的影响，MiBioGen联盟策划并分析了全基因组基因类型和来自18,340个个体(24个队列)的16S粪便微生物组数据。微生物组成在队列之间表现出高度的变异性：在超过95%的样本中，410个属中只有9个被检测到。一项关于宿主遗传变异与微生物分类群关系的全基因组关联研究确定了31个影响微生物组的基因座在全基因组显著(P<；5×10−8)的阈值上。乳糖酶(Lct)基因座在整个研究中均有显著意义(GWA信号P=1.2 8×10−2 0)，且与双歧杆菌的丰度呈年龄相关性。其他关联性较强(1.95×10−10<；P<；5×10−8)，但丰富了显示高遗传力的分类群以及在肠道和脑中表达的基因。一项表型相关研究和孟德尔随机化研究发现，微生物组特征基因在代谢、营养和环境领域丰富，并表明微生物组在溃疡性结肠炎和类风湿性关节炎中具有因果关系。
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 out of 410 genera were detected in more than 95% samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 31 loci affecting microbiome at a genome-wide significant (P<5×10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (GWAS signal P=1.28×10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95×10−10<P<5×10−8) 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 has causal effects in ulcerative colitis and rheumatoid arthritis.
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影响因子：
2
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan N;Thompson J
通讯作者：
Thompson J
影响因子：
4.2
作者：
Brooks JP;Edwards DJ;Harwich MD Jr;Rivera MC;Fettweis JM;Serrano MG;Reris RA;Sheth NU;Huang B;Girerd P;Vaginal Microbiome Consortium;Strauss JF 3rd;Jefferson KK;Buck GA
通讯作者：
Buck GA
影响因子：
5.9
作者：
Coluccia, Enza;Iardino, Patrizia;De Magistris, Laura
通讯作者：
De Magistris, Laura
影响因子：
14.9
作者：
Cole JR;Wang Q;Cardenas E;Fish J;Chai B;Farris RJ;Kulam-Syed-Mohideen AS;McGarrell DM;Marsh T;Garrity GM;Tiedje JM
通讯作者：
Tiedje JM
影响因子：
30.8
作者：
Bulik-Sullivan B;Finucane HK;Anttila V;Gusev A;Day FR;Loh PR;ReproGen Consortium;Psychiatric Genomics Consortium;Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3;Duncan L;Perry JR;Patterson N;Robinson EB;Daly MJ;Price AL;Neale BM
通讯作者：
Neale BM