Differential effect of genetic burden on disease phenotypes in Crohn's disease and ulcerative colitis: analysis of a North American cohort.
Differential effect of genetic burden on disease phenotypes in Crohn's disease and ulcerative colitis: analysis of a North American cohort.
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DOI：
10.1038/ajg.2013.464
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发表时间：
2014-03
影响因子：
9.8
通讯作者：
Xavier, Ramnik J.
中科院分区：
文献类型：
--
作者：
Ananthakrishnan, Ashwin N.;Huang, Hailiang;Nguyen, Deanna D.;Sauk, Jenny;Yajnik, Vijay;Xavier, Ramnik J.
克罗恩病（CD）和溃疡性结肠炎（UC）是一种慢性免疫介导的疾病，具有进行性复发缓解的过程。病程存在相当大的异质性，准确预测自然史一直具有挑战性。CD或UC遗传易感性增加的表型意义尚不清楚。我们研究的数据来源是从三级转诊中心招募的CD和UC患者的前瞻性队列。所有患者均在Illumina免疫芯片上进行基因分型。计算163个IBD风险基因座的遗传风险评分（GRS），并结合关联强度（对数比值比）和等位基因剂量，检查GRS四分位数的表型关联。我们的研究队列包括1，105例患者（697例CD，408例UC）。增加的遗传负担与CD的早期诊断年龄相关（P趋势=0.008）。最高GRS四分位数的患者可能比最低四分位数的患者早5年发病。遗传负担的增加也与CD的回肠受累相关（P趋势< 0.0001）。遗传负担的影响与NOD2基因座无关，并且在没有NOD2变异的人和从不吸烟的人中更强。一级亲属受累的UC患者具有较高的遗传负担，但GRS与UC的疾病表型无关。增加的遗传负担与CD而不是UC的早期诊断相关。IBD风险基因座的扩展组仅解释了疾病表型方差的一小部分，表明遗传学在预测自然史方面的临床效用有限。
Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases with a progressive relapsing remitting course. There is considerable heterogeneity in disease course and accurate prediction of natural history has been challenging. The phenotypic implication of increasing genetic predisposition to CD or UC is unknown. The data source for our study was a prospective cohort of CD and UC patients recruited from a tertiary referral center. All patients underwent genotyping on the Illumina Immunochip. A genetic risk score (GRS) incorporating strength of association (log odds ratio) and allele dose for each of the 163 IBD-risk loci was calculated and phenotypic associations examined across GRS quartiles. Our study cohort included 1,105 patients (697 CD, 408 UC). Increasing genetic burden was associated with earlier age of diagnosis of CD (Ptrend=0.008). Patients in the highest GRS quartile were likely to develop disease 5 years earlier than those in the lowest quartile. Increasing genetic burden was also associated with ileal involvement in CD (Ptrend < 0.0001). The effect of genetic burden was independent of the NOD2 locus and was stronger among those with no NOD2 variants, and in never smokers. UC patients with an involved first degree relative had a higher genetic burden, but GRS was not associated with disease phenotype in UC. Increasing genetic burden is associated with early age of diagnosis in CD but not UC. The expanded panel of IBD risk loci explains only a fraction of variance of disease phenotype suggesting limited clinical utility of genetics in predicting natural history.
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影响因子：
64.8
作者：
Khor, Bernard;Gardet, Agnes;Xavier, Ramnik J.
通讯作者：
Xavier, Ramnik J.
影响因子：
29.4
作者：
Abreu, MT;Taylor, KD;Yang, HY
通讯作者：
Yang, HY
影响因子：
3.7
作者：
Jung C;Colombel JF;Lemann M;Beaugerie L;Allez M;Cosnes J;Vernier-Massouille G;Gornet JM;Gendre JP;Cezard JP;Ruemmele FM;Turck D;Merlin F;Zouali H;Libersa C;Dieudé P;Soufir N;Thomas G;Hugot JP
通讯作者：
Hugot JP
影响因子：
4.9
作者：
Nimmo, Elaine R.;Prendergast, James G.;Satsangi, Jack
通讯作者：
Satsangi, Jack
影响因子：
9.8
作者：
Annese, V;Lombardi, G;Andriulli, A
通讯作者：
Andriulli, A