Predicting risk among non-respondents in prospective studies

Potential non-response bias was investigated in a follow-up study of 2,011 chronically disabled patients. 82.5% and 73.3% of the study subjects responded to self-administered mail questionnaires respectively at 6-month and 1-year follow-up. Information on employment status, the outcome of interest, of approximately 90% of the non-respondents was obtained from indirect sources. Employment rate was lower among the non-respondents than the respondents. Non-response was associated with age, social class, previous employment record, and the type of disability; but none of these characteristics were associated with the outcome. Out of the five known independent risk factors for unemployment, only one (incompletion of rehabilitation course) was associated with non-response. The employment rate among the respondents was also assessed according to the delay in response, that is the number of reminders sent to achieve response. The outcome among- the late respondents was similar to that among the nonrespondents. These data suggest that (a) risk estimates may be biased even when the response rate is greater than 80%, (b) the prevalence of risk factors among non-respondents may not indicate the presence or the degree of non-response bias, but (c) reliable estimates can be obtained from extrapolations of the rates among the respondents according to the delay in response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42663/1/10654_2004_Article_BF00152716.pd

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

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