It's always great to have someone join who likes to dive into the latest research abstracts for clues as to the cutting edge of discovery! I've taken the first article and included a quote from it below. It seems to be finding something that has been widely assumed to be lurking in whole genome analysis: that while ApoE 4 stands out like the steeple of a church as a risk factor, there are likely many other genes that are the equivalent of roofs rising above the skyline which can be protective or, in some case, additive to risk. Those other genes, as well as lifestyle factors, seem to be the invisible "X" factor that explains the wide variation in risk even among people with ApoE 4/4.
I've added the title of the articles you cited, so interested readers can decide to delve deeper. Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype
I checked the one allele which was mentioned as protective here:
Among ApoE4 carriers, the top SNP in ISYNA1, rs2303697, protected in all cohorts except CHARGE.
Unfortunately, it's not part of the 23&me analysis I had done. Sliced by ApoE Genotype, Whole Exome Data Yield New AD Variants
[John Hardy of University College, London] added that the error rate of AD diagnoses, upon which the AD risk associations rely, further complicates the findings.
Farrer said that all variants identified in ADSP will be put to the test in larger, whole genome sequencing cohorts. The Alzheimer’s Disease Genomic Consortium aims to sequence the whole genomes of at least quadruple the number of people included in the current ADSP WES analysis, Farrer said. “We are in the middle of an ongoing saga of filling in the genetic architecture of AD, which clearly is not accounted for by common variants.”
As an aside, you may want to check out our How-To guide
, which can aid in searching for citations of articles, quoting members when you reply to them, subscribing to topics of interest and other tips to save time.
I hope you continue to flag new articles for us to check out!