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Sequencing of over 100,000 individuals identifies multiple genes and rare variants associated with Crohns disease susceptibility

Aleksejs Sazonovs,Christine R. Stevens,Guhan R. Venkataraman,Kai Yuan, Brandon Avila,Maria T. Abreu,Tariq Ahmad,Matthieu Allez,Ashwin N. Ananthakrishnan,Gil Atzmon,Aris Baras,Jeffrey C. Barrett,Nir Barzilai,Laurent Beaugerie,Ashley Beecham,Charles N. Bernstein,Alain Bitton,Bernd Bokemeyer,Andrew Chan,Daniel Chung,Isabelle Cleynen,Jacques Cosnes,David J. Cutler,Allan Daly,Oriana M. Damas,Lisa W. Datta,Noor Dawany,Marcella Devoto,Sheila Dodge,Eva Ellinghaus,Laura Fachal,Martti Farkkila,William Faubion,Manuel Ferreira,Denis Franchimont,Stacey B. Gabriel,Michel Georges,Kyle Gettler,Mamta Giri,Benjamin Glaser,Siegfried Goerg,Philippe Goyette,Daniel Graham,Eija Hämäläinen,Talin Haritunians,Graham A. Heap,Mikko Hiltunen,Marc Hoeppner,Julie E. Horowitz,Peter Irving,Vivek Iyer,Chaim Jalas,Judith Kelsen,Hamed Khalili,Barbara S. Kirschner,Kimmo Kontula,Jukka T. Koskela,Subra Kugathasan,Juozas Kupcinskas,Christopher A. Lamb,Matthias Laudes,Adam P. Levine, James Lewis,Claire Liefferinckx, Britt-Sabina Loescher,Edouard Louis,John Mansfield,Sandra May,Jacob L. McCauley,Emebet Mengesha,Myriam Mni,Paul Moayyedi,Christopher J. Moran,Rodney Newberry,Sirimon O’Charoen,David T. Okou,Bas Oldenburg,Harry Ostrer,Aarno Palotie,Joel Pekow,Inga Peter,Marieke J. Pierik,Cyriel Y. Ponsioen,Nikolas Pontikos,Natalie Prescott,Ann E. Pulver,Souad Rahmouni,Daniel L. Rice,Päivi Saavalainen,Bruce Sands,R. Balfour Sartor,Elena R. Schiff,Stefan Schreiber, L. Philip Schuum,Anthony W. Segal,Philippe Seksik,Rasha Shawky,Shehzad Z. Sheikh,Mark Silverberg,Alison Simmons,Jurgita Skeiceviciene,Harry Sokol,Matthew Solomonson,Hari Somineni,Dylan Sun,Stephan Targan,Dan Turner,Holm H. Uhlig,Andrea E. van der Meulen,Severine Vermeire,Sare Verstockt,Michiel D. Voskuil,Harland S. Winter, Justine Young,Richard H. Duerr,Andre Franke,Steven R. Brant,Judy Cho,Rinse K. Weersma,Miles Parkes,Ramnik Xavier,Manuel A. Rivas,John D. Rioux,Dermot McGovern,Hailiang Huang,Carl A. Anderson,Mark J. Daly

medRxiv(2021)

引用 5|浏览57
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摘要
Genome-wide association studies (GWAS) have identified hundreds of loci associated with Crohns disease (CD); however, as with all complex diseases, deriving pathogenic mechanisms from these non-coding GWAS discoveries has been challenging. To complement GWAS and better define actionable biological targets, we analysed sequence data from more than 30,000 CD cases and 80,000 population controls. We observe rare coding variants in established CD susceptibility genes as well as ten genes where coding variation directly implicates the gene in disease risk for the first time.
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关键词
crohns disease susceptibility,multiple genes,rare variants
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