Abstract
Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10−04, Sweden P=7.44 × 10−05). Combining all five European data sets – Central Europe, Italy, Spain, Poland and Sweden – the insertion is achalasia associated with Pcombined=1.67 × 10−35. In addition, we observe that the frequency of the insertion shows a geospatial north–south gradient. The insertion is less common in northern (around 6–7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.
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Acknowledgements
We thank all patients for participating in this study. We acknowledge our collaborating clinical partners, all colleagues who contributed to the patient’s recruitment, our laboratory technicians and colleagues responsible for database management. We thank the Type I Diabetes Genetics Consortium (T1DGC) for data access. IG, MK and JS received support for this work from the Deutsche Forschungsgemeinschaft (DFG), individual grants GO 1795/1-1, KN 378/2-1 and SCHU 1596/5-1. MMN received support for this work from the Alfried Krupp von Bohlen und Halbach-Stiftung, and is a member of the DFG funded Excellence Cluster ImmunoSensation. PIWdB is the recipient of a Vernieuwingsimpuls VIDI Award from the Netherlands Organization for Scientific Research (NWO). MMW is supported by a postdoctoral fellowship of the Fund for Scientific Research (FWO) Flanders, Belgium. GEB is supported by a grant from the Research Foundation – Flanders (FWO, Odysseus program). AT is supported by grants from the Erling-Persson Family Foundation, Sweden. The Heinz Nixdorf Recall cohort was established with the generous support of the Heinz Nixdorf Foundation, Germany.
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Becker, J., Haas, S., Mokrowiecka, A. et al. The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north–south gradient among Europeans. Eur J Hum Genet 24, 1228–1231 (2016). https://doi.org/10.1038/ejhg.2015.262
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DOI: https://doi.org/10.1038/ejhg.2015.262
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