4.8 Article

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

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NATURE GENETICS
卷 42, 期 12, 页码 1118-+

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NATURE PUBLISHING GROUP
DOI: 10.1038/ng.717

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资金

  1. Medical Research Council [G0800675, G0600329, G0800759] Funding Source: Medline
  2. NCRR NIH HHS [M01-RR00425, M01 RR000425] Funding Source: Medline
  3. NHLBI NIH HHS [N01HC85086, N01-HC-85082, R01 HL087652, N01-HC-85084, N01 HC-55222, N01-HC-85083, N01-HC-75150, N01-HC-85080, N01 HC015103, N01-HC-85081, N01 HC045133, U01 HL080295, N01HC75150, N01-HC-85086, N01-HC-85079, N01HC85079, N01 HC035129, N01-HC-85085, N01HC55222] Funding Source: Medline
  4. NIAMS NIH HHS [K08 AR055688-03, K08 AR055688-04, K08 AR055688-01A1S1, K08 AR055688] Funding Source: Medline
  5. NIDDK NIH HHS [R21 DK084554, U01 DK062420, DK 063491, DK064869, DK76984, R03 DK076984, P30 DK063491, U01 DK062422, DK062422, DK062420, P01 DK046763, U01 DK062423, DK062429, P01-DK046763, U01 DK062429, DK062423, P30 DK043351, DK062432, DK062413, DK069513, U01 DK062413, K23 DK069513, R01 DK064869, DK062431, DK084554, U01 DK062431, U01 DK062432] Funding Source: Medline
  6. Wellcome Trust [089120, WT089120/Z/09/Z] Funding Source: Medline
  7. Chief Scientist Office [CZB/4/540] Funding Source: Medline
  8. MRC [G0800675, G0600329, G0800759] Funding Source: UKRI
  9. Chief Scientist Office [CZB/4/540] Funding Source: researchfish
  10. Medical Research Council [G0800675, G0800759, G0600329] Funding Source: researchfish

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We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

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