Alzheimer disease is a huge and growing societal problem with upwards of 35% of the population over the age of 80 developing the disease. AD results in a loss of memory, the ability to make reasoned and sound decisions, and ultimately the inability to take care of oneself. AD has an impact not only on the sufferer, but their caretakers and loved ones, who must take on a costly and time-consuming burden of care. AD is found in virtually all racial (...) and ethnic groups. Genetic influences on AD are substantial, and there has been a 30 year history of both success and failure. Mutations for rare early onset forms of the disease have been identified, but this information has not yet led to an effective treatment. Multiple common genetic variations have also been identified, and have led to new insights into the potential role of microglia cells in addition to neuronal cells in the brain. Despite intensive efforts, a significant portion of the genetic etiology of AD remains unknown and must be identified. (shrink)

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 associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease 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 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. © 2012 Nature America, Inc. All rights reserved. (shrink)