Large-scale association analyses identify host factors influencing human gut microbiome composition
Kurilshikov A., Medina-Gomez C., Bacigalupe R., Radjabzadeh D., Wang J., Demirkan A., Roy CL., Raygoza Garay JA., Finnicum C., Liu X., Zhernakova D., Bonder MJ., Hansen T., Frost F., Rühlemann M., Turpin W., Moon J-Y., Kim H-N., Lüll K., Barkan E., Shah S., Fornage M., Szopinska-Tokov J., Wallen Z., Borisevich D., Agreus L., Andreasson A., Bang C., Bedrani L., Bell J., Bisgaard H., Boehnke M., Boomsma D., Burk R., Claringbould A., Croitoru K., Davies G., van Duijn C., Duijts L., Falony G., Fu J., van der Graaf A., Hansen T., Homuth G., Hughes D., Ijzerman R., Jackson M., Jaddoe VWV., Joossens M., Jørgensen T., Keszthelyi D., Knight R., Laakso M., Laudes M., Launer L., Lieb W., Lusis A., Masclee AAM., Moll H., Mujagic Z., Qibin Q., Rothschild D., Shin H., Sørensen S., Steves C., Thorsen J., Timpson N., Tito R., Vieira-Silva S., Völker U., Völzke H., Võsa U., Wade K., Walter S., Watanabe K., Weiss S., Weiss F., Weissbrod O., Westra H-J., Willemsen G., Payami H., Jonkers DMAE., Vasquez AA., de Geus EJC., Meyer K., Stokholm J., Segal E., Org E., Wijmenga C., Kim H-L., Kaplan R., Spector T., Uitterlinden A., Rivadeneira F., Franke A., Lerch M., Franke L., Sanna S., D’Amato M., Pedersen O., Paterson A., Kraaij R., Raes J., Zhernakova A.
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