小柯机器人

荷兰格罗宁根大学医学中心Alexandra Zhernakova、Alexander Kurilshikov等研究人员合作，通过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。这一研究成果于2021年1月18日在线发表在国际学术期刊《自然—遗传学》上。

为了研究宿主遗传学对肠道微生物组组成的影响，MiBioGen联盟组织并分析了来自18,340个个体（24个队列）的全基因组基因型和16S粪便微生物组数据。微生物组成在整个队列中表现出高度的可变性：在超过95％的样本中仅检测到410属中的9个。关于微生物分类群的宿主遗传变异的全基因组关联研究确定了在整个基因组显著（P<5×10^-8）阈值下影响微生物组的31个基因座。

一个基因座，即乳糖酶（LCT）基因座，在整个研究中具有重要意义（全基因组关联研究信号：P=1.28×10^-20），并且与双歧杆菌的丰度呈年龄依赖性。其他关联是暗示性的（1.95×10^-10<P<5×10^-8），但丰富了显示高遗传力的分类单元以及在肠和脑中表达的基因。

一项全基因组关联研究和孟德尔随机研究确定了代谢、营养和环境领域中微生物组特征基因座的富集，并表明微生物组可能在溃疡性结肠炎和类风湿性关节炎中具有因果关系。

附：英文原文

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

Author: Alexander Kurilshikov, Carolina Medina-Gomez, Rodrigo Bacigalupe, Djawad Radjabzadeh, Jun Wang, Ayse Demirkan, Caroline I. Le Roy, Juan Antonio Raygoza Garay, Casey T. Finnicum, Xingrong Liu, Daria V. Zhernakova, Marc Jan Bonder, Tue H. Hansen, Fabian Frost, Malte C. Rhlemann, Williams Turpin, Jee-Young Moon, Han-Na Kim, Kreete Lll, Elad Barkan, Shiraz A. Shah, Myriam Fornage, Joanna Szopinska-Tokov, Zachary D. Wallen, Dmitrii Borisevich, Lars Agreus, Anna Andreasson, Corinna Bang, Larbi Bedrani, Jordana T. Bell, Hans Bisgaard, Michael Boehnke, Dorret I. Boomsma, Robert D. Burk, Annique Claringbould, Kenneth Croitoru, Gareth E. Davies, Cornelia M. van Duijn, Liesbeth Duijts, Gwen Falony, Jingyuan Fu, Adriaan van der Graaf, Torben Hansen, Georg Homuth, David A. Hughes, Richard G. Ijzerman, Matthew A. Jackson, Vincent W. V. Jaddoe, Marie Joossens, Torben Jrgensen, Daniel Keszthelyi, Rob Knight, Markku Laakso, Matthias Laudes, Lenore J. Launer, Wolfgang Lieb, Aldons J. Lusis, Ad A. M. Masclee, Henriette A. Moll, Zlatan Mujagic, Qi Qibin, Daphna Rothschild

Issue&Volume: 2021-01-18

Abstract: 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<5×108) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P=1.28×1020), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95×1010<P<5×108) 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.

DOI: 10.1038/s41588-020-00763-1

Source: https://www.nature.com/articles/s41588-020-00763-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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