Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis.
Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis.
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DOI：
10.1016/j.jaci.2014.07.021
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发表时间：
2014-11
影响因子：
14.2
通讯作者：
Rothenberg, Marc E.
中科院分区：
文献类型：
--
作者：
Alexander, Eileen S.;Martin, Lisa J.;Collins, Margaret H.;Kottyan, Leah C.;Sucharew, Heidi;He, Hua;Mukkada, Vincent A.;Succop, Paul A.;Abonia, J. Pablo;Foote, Heather;Eby, Michael D.;Grotjan, Tommie M.;Greenler, Alexandria J.;Dellon, Evan S.;Demain, Jeffrey G.;Furuta, Glenn T.;Gurian, Larry E.;Harley, John B.;Hopp, Russell J.;Kagalwalla, Amir;Kaul, Ajay;Nadeau, Kari C.;Noel, Richard J.;Putnam, Philip E.;von Tiehl, Karl F.;Rothenberg, Marc E.
关键词：
嗜酸性食管炎(EoE)是一种慢性抗原驱动的变态反应性炎症性疾病，可能涉及遗传和环境因素的相互作用，但它们各自对遗传力的贡献尚不清楚。量化EoE家族性聚集性与基因和环境相关的风险。家族史来自914名EoE先证者的医院队列(n=2192名一级“核心家庭”亲属)和新的国际单卵和双卵双胞胎/三胞胎登记(n=63名EoE“双胞胎”先证者)。对发病频率、复发风险比(RRR)、遗传率和双胞胎一致性进行评估。对环境暴露进行了初步检查。对以核心家庭为基础的队列的分析表明，先证者的一级亲属的EoE发生率为1.8%(未经调整)和2.3%(经性别调整)。根据家庭关系的不同，RRR从10-不等，兄弟(64.0p=0.04)、父亲(42.9p=0.004)和男性(50.7p<；0.001)分别高于姐妹、母亲和女性。其他兄弟姐妹发生EoE的风险为2.4%。在核心家系中，基因和共同环境相结合的遗传度(Hgc2)为72.00±2.7%(p<；0.001)。在双生子队列中，遗传遗传力为14.5%±4.0%(p<；0.001)，共同家庭环境对表型变异的贡献率为81.0%±4%(p<；0.001)。MZ同卵双胞胎的先兆符合率为57.9±9.5%，DZ为36.4±9.3%(p=0.11)。双胞胎出生体重差异较大(p=0.01)、母乳喂养(p=0.15)和秋季出生季节(p=0.02)与疾病状况的双胞胎不协调有关。与普通人群相比，EOE复发风险比增加了10倍。亲属的EoE为1.8%-2.4%，取决于关系和性别。核心家族遗传率较高(72.0%)。然而，双生子队列分析显示，共同环境(81.0%)比加性遗传遗传力(14.5%)起到了很大的作用。
Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. To quantify risk associated with genes and environment on familial clustering of EoE. Family history was obtained from a hospital-based cohort of 914 EoE probands, (n=2192 first-degree “Nuclear-Family” relatives) and the new international registry of monozygotic and dizygotic twins/triplets (n=63 EoE “Twins” probands). Frequencies, recurrence risk ratios (RRRs), heritability and twin concordance were estimated. Environmental exposures were preliminarily examined. Analysis of the Nuclear-Family–based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10–64, depending on the family relationship, and were higher in brothers (64.0; p=0.04), fathers (42.9; p=0.004) and males (50.7; p<0.001) compared to sisters, mothers and females, respectively. Risk of EoE for other siblings was 2.4%. In the Nuclear-Families, combined gene and common environment heritability (hgc2) was 72.0±2.7% (p<0.001). In the Twins cohort, genetic heritability was 14.5±4.0% (p<0.001), and common family environment contributed 81.0±4% (p<0.001) to phenotypic variance. Proband-wise concordance in MZ co-twins was 57.9±9.5% compared to 36.4±9.3% in DZ (p=0.11). Greater birth-weight difference between twins (p=0.01), breastfeeding (p=0.15) and Fall birth season (p=0.02) were associated with twin discordance in disease status. EoE recurrence risk ratios are increased 10–64-fold compared with the general population. EoE in relatives is 1.8–2.4%, depending upon relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, Twins cohort analysis revealed a powerful role for common environment (81.0%) compared with additive genetic heritability (14.5%).
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DOI：
10.1016/j.jaci.2010.10.007
发表时间：
2010-12
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
NIAID-Sponsored Expert Panel;Boyce JA;Assa'ad A;Burks AW;Jones SM;Sampson HA;Wood RA;Plaut M;Cooper SF;Fenton MJ;Arshad SH;Bahna SL;Beck LA;Byrd-Bredbenner C;Camargo CA Jr;Eichenfield L;Furuta GT;Hanifin JM;Jones C;Kraft M;Levy BD;Lieberman P;Luccioli S;McCall KM;Schneider LC;Simon RA;Simons FE;Teach SJ;Yawn BP;Schwaninger JM
通讯作者：
Schwaninger JM
影响因子：
4.8
作者：
Lim, Eun Jin;Lu, Thomas X.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
29.4
作者：
Akei, HS;Mishra, A;Rothenberg, ME
通讯作者：
Rothenberg, ME
影响因子：
0.9
作者：
Boomsma, Dorret I.;Cacioppo, John T.;Clark, Shaunna
通讯作者：
Clark, Shaunna
DOI：
10.1016/j.jaci.2010.10.039
发表时间：
2011-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Blanchard C;Stucke EM;Rodriguez-Jimenez B;Burwinkel K;Collins MH;Ahrens A;Alexander ES;Butz BK;Jameson SC;Kaul A;Franciosi JP;Kushner JP;Putnam PE;Abonia JP;Rothenberg ME
通讯作者：
Rothenberg ME