New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Comment: The Performance of Performance

As Bill Starbuck observes, measures of performance do not perform very well. They are compromised by measurement and data errors, which complicates statistical inferences. Nevertheless, performance measurements are needed and may be necessary for guiding organizational changes. Although the errors that Starbuck notes are important, there are other considerations that may be more damaging for most uses of performance data. Most users of performance measurements are interested in what they reveal about behaviors and capabilities. They use performance measures as signal of some underlying latent trait, such as leadership ability of competitive advantage. Seen from this perspective, performance measures are plagued by several other sources of error and bias in addition to those discussed by Starbuck