Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Herkunft des Rohmaterials

International audienc

Satellite observations show no net change in the percentage of supraglacial debris-covered area in northern Pakistan from 1977 to 2014

Spatial evolution of supraglacial debris cover on mountain glaciers is a largely unmonitored and poorly understood phenomenon that directly affects glacier melt. Supraglacial debris cover for 93 glaciers in the Karakoram, northern Pakistan, was mapped from Landsat imagery acquired in 1977, 1998, 2009 and 2014. Surge-type glaciers occupy 41% of the study area and were considered separately. The time series of debris-covered surface area change shows a mean value of zero or near-zero change for both surging and non-surging glaciers. An increase in debris-covered area is often associated with negative regional mass balances. We extend this logic to suggest that the stable regional mass balances in the Karakoram explain the zero or near-zero change in debris-covered area. This coupling of trends combined with our 37 year time series of data suggests the Karakoram anomaly extends further back in time than previously known.ISSN:0022-1430ISSN:1727-565

The Neolithic reaping knives from Egolzwil 3: A Mediterranean technical tradition in the late 5th millennium Swiss Neolithic

The study of the use-wear marks on the Neolithic reaping knives from the site of Egolzwil 3 (Switzerland, late fifth millennium cal BC) shows that these tools were used to reap cereals by cutting the stems near the ground. The stems were gathered together using the pointed distal end, held in the free hand and cut with the flint blade, in what we term a two-stage reaping method. These types of sickles or reaping knives are found at Neolithic sites in the northern Mediterranean (centre and north of the Iberian Peninsula, Provence in France and continental Italy) from the mid-sixth millennium, in the context of the early Neolithic Cardial Culture, and lasted until the early fourth millennium. Within the tradition of twostage reaping knives, the Egolzwil type would have been adapted to reaping at a low height in very dense cereal fields. These tools show that the Neolithic groups in the Swiss central plain belonged to the circle of northern Mediterranean farming technical traditions, in their northernmost expression, in contact with the groups in south Germany who reaped with curved sickles whose flint elements were inserted obliquely.This study was carried out thanks to the collaboration of the Museum of Zürich and Archaeological Centre of Lucerne Canton. It formed part of the research performed in the framework of the R+D project HAR2011-23149, funded by the Ministry of Economy and Competitiveness of the Government of Spain and the Agrest II Research Group.Peer reviewe

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rarePRSS1,CFTR, andSPINK1variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated atPRSS1-PRSS2(1×10-12) and x-linkedCLDN2(p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). ThePRSS1variant affects susceptibility by altering expression of the primary trypsinogen gene. TheCLDN2risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male)CLDN2genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07