Publications by authors named "B Vardarajan"
The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's Disease and Related Dementias (AD/ADRD) by sequencing whole genomes of affected participants and age-matched cognitive controls from diverse populations. The Genome Center for Alzheimer's Disease (GCAD) processed whole-genome sequencing data from 36,361 ADSP participants, including 35,014 genetically unique participants of which 45% are from non-European ancestry, across 17 cohorts in 14 countries in this fourth release (R4). This sequencing effort identified 387 million bi-allelic variants, 42 million short insertions/deletions, and 2.
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- Hidden biases in non-randomized studies challenge the identification of causal protein biomarkers for Alzheimer's disease, and traditional methods can lead to misleading results.
- The MR-SPI method enhances Mendelian randomization by selecting valid pQTL instruments, addressing some of these biases and integrating structural predictions from AlphaFold3.
- Using data from over 500,000 individuals, researchers identified seven proteins with structural changes linked to Alzheimer's, contributing to understanding the disease's causes and potential treatment targets.
Article Synopsis
- Genetic research on Alzheimer's disease (AD) has largely concentrated on amyloid-β (Aβ), while this study focuses on understanding the genetic basis of tau pathology to uncover new pathways related to AD.
- A genome-wide association study (GWAS) was conducted using data from the A4 and ADNI studies to analyze genetic variants linked to tau pathology, finding two significant loci and pinpointing certain genes associated with tau deposition.
- Mendelian randomization analyses suggest that the LRRFIP1 protein may have a causal relationship with tau pathology, while the polygenic risk scores showed strong associations with amyloid pathology but not with tau pathology.
Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer's disease (AD). CD33, an immunomodulatory transmembrane sialic acid binding protein expressed on myeloid cells, was identified as one such genetic risk factor associated with Alzheimer's disease. Several studies explored the molecular outcomes of genetic variation at the locus.
View Article and Find Full Text PDFBackground: Few rare variants have been identified in genetic loci from genome-wide association studies (GWAS) of Alzheimer's disease (AD), limiting understanding of mechanisms, risk assessment, and genetic counseling.
Methods: Using genome sequencing data from 197 families in the National Institute on Aging Alzheimer's Disease Family Based Study and 214 Caribbean Hispanic families, we searched for rare coding variants within known GWAS loci from the largest published study.
Results: Eighty-six rare missense or loss-of-function (LoF) variants completely segregated in 17.