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

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 8 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 to southern Europeans (around 16% in patients and 8% in controls from Italy) and shows a stronger attributable risk (AR) in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00010000858	Achalasia cases & controls		8151

Publications	Citations
The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans. Becker J, Haas SL, Mokrowiecka A, Wasielica-Berger J, Ateeb Z, Bister J, Elbe P, Kowalski M, Gawron-Kiszka M, Majewski M, Mulak A, Janiak M, Wouters MM, Schwämmle T, Hess T, Veits L, Niebisch S, Santiago JL, de León AR, de la Serna JP, Urcelay E, Annese V, Latiano A, Fumagalli U, Rosati R, Laghi L, Cuomo R, Lenze F, Sarnelli G, Müller M, von Rahden BH, Wijmenga C, Lang H, Czene K, Hall P, de Bakker PI, Vieth M, Nöthen MM, Schulz HG, Adrych K, Gąsiorowska A, Paradowski L, Wallner G, Boeckxstaens GE, Gockel I, Hartleb M, Kostic S, Dziurkowska-Marek A, Lindblad M, Nilsson M, Knapp M, Thorell A, Marek T, Dąbrowski A, Małecka-Panas E, Schumacher J. Eur J Hum Genet 24: 2016 1228-1231	12

Publications

Citations

The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.
Becker J, Haas SL, Mokrowiecka A, Wasielica-Berger J, Ateeb Z, Bister J, Elbe P, Kowalski M, Gawron-Kiszka M, Majewski M, Mulak A, Janiak M, Wouters MM, Schwämmle T, Hess T, Veits L, Niebisch S, Santiago JL, de León AR, de la Serna JP, Urcelay E, Annese V, Latiano A, Fumagalli U, Rosati R, Laghi L, Cuomo R, Lenze F, Sarnelli G, Müller M, von Rahden BH, Wijmenga C, Lang H, Czene K, Hall P, de Bakker PI, Vieth M, Nöthen MM, Schulz HG, Adrych K, Gąsiorowska A, Paradowski L, Wallner G, Boeckxstaens GE, Gockel I, Hartleb M, Kostic S, Dziurkowska-Marek A, Lindblad M, Nilsson M, Knapp M, Thorell A, Marek T, Dąbrowski A, Małecka-Panas E, Schumacher J. Eur J Hum Genet 24: 2016 1228-1231