Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis

被引：172
|
作者：
Alexander, Eileen S. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ,12 ]
Martin, Lisa J. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Collins, Margaret H. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Kottyan, Leah C. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Sucharew, Heidi [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
He, Hua [5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Mukkada, Vincent A. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Succop, Paul A. [1 ,2 ,3 ,4 ]
Abonia, J. Pablo [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Foote, Heather [5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Eby, Michael D. [5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Grotjan, Tommie M. [5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Greenler, Alexandria J. [5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Dellon, Evan S. [13 ]
Demain, Jeffrey G. [14 ]
Furuta, Glenn T. [15 ]
Gurian, Larry E. [16 ]
Harley, John B. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ,17 ]
Hopp, Russell J. [18 ]
Kagalwalla, Amir [19 ,20 ]
Kaul, Ajay [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
Nadeau, Kari C. [21 ,22 ,23 ]
Noel, Richard J. [24 ,25 ]
Putnam, Philip E. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
von Tiehl, Karl F. [26 ]
Rothenberg, Marc E. [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 ]
机构：
[1] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA
[3] Univ Cincinnati, Coll Med, Dept Pathol, Cincinnati, OH USA
[4] Univ Cincinnati, Coll Med, Dept Lab Med, Cincinnati, OH USA
[5] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA
[6] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA
[7] Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA
[8] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Div Rheumatol, Cincinnati, OH 45229 USA
[9] Cincinnati Childrens Hosp Med Ctr, Div Gastroenterol, Cincinnati, OH 45229 USA
[10] Cincinnati Childrens Hosp Med Ctr, Div Hepatol & Nutr, Cincinnati, OH 45229 USA
[11] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA
[12] Xavier Univ, Dept Hlth Serv Adm, Cincinnati, OH 45207 USA
[13] Univ N Carolina, Sch Med, Esophageal Dis & Swallowing, Div Gastroenterol & Hepatol, Chapel Hill, NC USA
[14] Allergy Asthma & Immunol Ctr Alaska, Anchorage, AK USA
[15] Univ Colorado, Sch Med, Digest Hlth Inst, Gastrointestinal Eosinophil Dis Program,Childrens, Aurora, CO USA
[16] Ferrell Duncan Clin & CoxHlth, Springfield, MO USA
[17] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA
[18] Creighton Univ, Dept Pediat, Div Allergy & Immunol, Omaha, NE 68178 USA
[19] Ann & Robert H Lurie Childrens Hosp Chicago, Div Gastroenterol Hepatol & Nutr, Chicago, IL USA
[20] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA
[21] Stanford Med Sch, Stanford, CA USA
[22] Stanford Med Ctr, Div Allergy & Immunol, Stanford, CA USA
[23] Lucille Packard Childrens Hosp, Stanford, CA USA
[24] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA
[25] Med Coll Wisconsin, Milwaukee, WI 53226 USA
[26] Huntington Mem Hosp, Pasadena, CA USA
来源：
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2014年 / 134卷 / 05期
基金：
美国国家卫生研究院;
关键词：
Eosinophilia; food allergy; medical genetics; twins; immune system diseases; heritability; gene-environment interaction; drug hypersensitivity; gastrointestinal diseases; skin diseases; MISSING HERITABILITY; MOLECULAR CHARACTERIZATION; PROVIDES INSIGHT; LINKAGE ANALYSIS; CROHNS-DISEASE; EARLY-LIFE; ASSOCIATION; EXPRESSION; EXPOSURE; ANTIBIOTICS;
D O I：
10.1016/j.jaci.2014.07.021
中图分类号：
R392 [医学免疫学];
学科分类号：
100102 ;
摘要：
Background: 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. Objective: To quantify the risk associated with genes and environment on familial clustering of EoE. Methods: Family history was obtained from a hospital-based cohort of 914 EoE probands (n = 2192 first-degree "Nuclear-Family" relatives) and an 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. Results: 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 to 64, depending on the family relationship, and were higher in brothers (64.0; P = .04), fathers (42.9; P = .004), and males (50.7; P < .001) than in sisters, mothers, and females, respectively. The risk of EoE for other siblings was 2.4%. In the Nuclear-Family cohort, combined gene and common environment heritability was 72.0% 6 2.7% (P < .001). In the Twins cohort, genetic heritability was 14.5% +/- 4.0% (P < .001), and common family environment contributed 81.0% +/- 4% (P < .001) to phenotypic variance. Probandwise concordance in monozygotic co-twins was 57.9% +/- 9.5% compared with 36.4% +/- 9.3% in dizygotic co-twins (P = .11). Greater birth weight difference between twins (P = .01), breast-feeding (P = .15), and fall birth season (P = .02) were associated with twin discordance in disease status. Conclusions: EoE RRRs are increased 10- to 64-fold compared with the general population. EoE in relatives is 1.8% to 2.4%, depending on relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, the Twins cohort analysis revealed a powerful role for common environment (81.0%) compared with additive genetic heritability (14.5%).
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页码：1084 / +
页数：10
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