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- Gehlen, J., et al.
(author)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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In: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Journal article (peer-reviewed)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 2. |
- Rozensztrauch, A., et al.
(author)
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Reliability and Validity of the Polish Version of the Esophageal-Atresia-Quality-of-Life Questionnaires to Assess Condition-Specific Quality of Life in Children and Adolescents Born with Esophageal Atresia
- 2022
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 19:13
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Journal article (peer-reviewed)abstract
- Aim: This study reports the reliability and validity of the Polish version of the Esophageal Atresia Quality of Life (EA-QOL) questionnaires, which were originally developed in Sweden and Germany. Methods: A total of 50 families of children (23 aged 2 to 7, and 27 aged 8 to 17) with EA/TEF (esophageal atresia/tracheoesophageal fistula) participated in the study. The development and validation of the Polish version of the EA-QOL involved forward-backward translation of the survey items following the guidelines for cross-cultural translation, cognitive debriefing and evaluation of psychometric properties, including assessment of internal and retest reliability, linguistic validity, content validity, known-group validity and convergent validity. The medical records of patients and standardized questionnaires were used to obtain clinical data. The level of significance was p < 0.05. Results: The Polish versions of the EA-QOL questionnaires demonstrated strong linguistic and content validity, are slightly discriminative for esophageal and respiratory problems, but do not show convergent validity with the PedsQL 4.0 generic core scales. In terms of reliability, the internal consistency of the subscale and total scale of Polish versions as measured by Cronbach's alpha is good, and retest reliability is excellent. Conclusions: The Polish versions of the EA-QOL questionnaires meet most psychometric criteria that confirm the EA-QOL questionnaires' reliability and validity. This study enables application of these questionnaires in future research among children with EA in Poland and participation in international multicenter studies focusing on advancing knowledge of condition-specific QOL in this population. Future cross-cultural research using larger sample sizes is still needed to better address the relationship between condition-specific and generic QOL, as well as the discriminative ability of the EA-QOL questionnaires.
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