The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north–south gradient among Europeans

Jessica Becker, Stephan L. Haas, Anna Mokrowiecka, Justyna Wasielica-Berger, Zeeshan Ateeb, Jonna Bister, Peter Elbe, Marek Kowalski, Magdalena Gawron-Kiszka, Marek Majewski, Agata Mulak, Maria Janiak, Mira M. Wouters, Till Schwämmle, Timo Hess, Lothar Veits, Stefan Niebisch, José L. Santiago, Antonio Ruiz De León, Julio Pérez De La SernaElena Urcelay, Vito Annese, Anna Latiano, Uberto Fumagalli Romario, Riccardo Rosati, Luigi Andrea Giuseppe Laghi, Rosario Cuomo, Frank Lenze, Giovanni Sarnelli, Michaela Müller, Burkhard H A von Rahden, Cisca Wijmenga, Hauke Lang, Kamila Czene, Per Hall, P. de Bakker, Michael Vieth, Markus M. Nöthen, Henning G. Schulz, Krystian Adrych, Anita Gąsiorowska, Leszek Paradowski, Grzegorz Wallner, Guy E. Boeckxstaens, Ines Gockel, Marek Hartleb, Srdjan Kostic, Anna Dziurkowska-Marek, Mats Lindblad, Magnus Nilsson, Michael Knapp, Anders Thorell, Tomasz Marek, Andrzej Dąbrowski, Ewa Malecka-Panas, Johannes Schumacher

Research output: Contribution to journalArticlepeer-review


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.European Journal of Human Genetics advance online publication, 6 January 2016; doi:10.1038/ejhg.2015.262.

Original languageEnglish
JournalEuropean Journal of Human Genetics
Publication statusAccepted/In press - Jan 6 2016

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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