Lili Wang

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Nature Communications · 2021 · 332 citations

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD…

Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel

JAMA Neurology · 2020 · 271 citations

Importance: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated. Objective: T…

Genetic variants and functional pathways associated with resilience to Alzheimer’s disease

Brain · 2020 · 141 citations

Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing b…

Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset

Alzheimer s & Dementia · 2025-05-01 · 19 citations

INTRODUCTION: The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's disease and related dementias (ADRD) by integrating whole genome sequencing (WGS) with other genetic, phenotypic, and harmonized datasets from diverse populations. METHODS: The Genome Center for Alzheimer's Disease (GCAD) uniformly processed WGS from 36,361 ADSP samples, including 35,014 genetically unique participants of which 45% are from non-European a…

Structural variation detection and association analysis of whole‐genome‐sequence data from 16,543 Alzheimer's disease sequencing project subjects

Alzheimer s & Dementia · 2025-06-01 · 5 citations

Abstract INTRODUCTION The role of structural variations (SVs) in Alzheimer's disease (AD) remains understudied. METHODS We analyzed whole‐genome sequencing data from the Alzheimer's Disease Sequencing Project ( N = 16,543) and identified 400,234 (168,223 high‐quality) SVs. Laboratory validation yielded a sensitivity of 82% (85% for high‐quality). RESULTS We found a burden of singletons (odds ratio [OR] = 1.07, p = 0.0017) and homozygous deletions (OR = 1.14, p < 0.0001) in cases. On AD genes,…