Evaluating the association of genotype and cognitive resilience in SuperAgers.

Importance: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary memory are underexplored in large, racially diverse cohorts.

Objective: To determine the frequency of genotypes in non-Hispanic Black and non-Hispanic White SuperAgers compared to middle-aged (ages 50-64), old (ages 65-79), and oldest-old (ages 80+) controls and Alzheimer's disease (AD) dementia cases.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.

- a large-scale dataset of 3D medical shapes for computer vision.

Objectives: The shape is commonly used to describe the objects. State-of-the-art algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from the growing popularity of ShapeNet (51,300 models) and Princeton ModelNet (127,915 models).

Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset.

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.

CHARMER: detecting and harmonizing high-confidence chromatin interactions across tissues and Hi-C protocols.

Motivation: Chromatin conformation capture experiments (CCC), such as Hi-C and Capture Hi-C (CHiC) work to elucidate the three-dimensional organization of the genome and the underlying epigenetic regulatory structures within. CCC experiments produce large amounts of FASTQ sequencing data with a substantial amount of technical noise and require sophisticated computational pipelines in order to extract meaningful results. Large-scale CCC data repositories like 4D Nucleome and ENCODE mostly provide raw contact information but lack annotated, statistically significant interaction data suitable for downstream genetic and genomic analyses.

Cerebral amyloid angiopathy impacts neurofibrillary tangle burden and cognition.

Cerebral amyloid angiopathy commonly co-occurs with amyloid β plaques and neurofibrillary degeneration and is proposed to contribute to cognitive impairment. However, the interplay among these pathologic changes of Alzheimer disease is not well understood. Here we replicate and extend findings of a recent study that suggested the association of cerebral amyloid angiopathy and cognitive impairment is mediated by neurofibrillary degeneration.

NIAGADS: A Comprehensive National Data Repository for Alzheimer's Disease and Related Dementia Genetics and Genomics Research.

NIAGADS is the National Institute on Aging (NIA) designated national data repository for human genetics research on Alzheimer's Disease and related dementia (ADRD). NIAGADS maintains a high-quality data collection for ADRD genetic/genomic research and supports genetics data production and analysis. NIAGADS hosts whole genome and exome sequence data from the Alzheimer's Disease Sequencing Project (ADSP) and other genotype/phenotype data, encompassing 209,000 samples.

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes.

Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer's disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored.

Balancing the efforts of chart review and gains in PRS prediction accuracy: An empirical study.

Objective: Phenotypic misclassification in genetic association analyses can impact the accuracy of PRS-based prediction models. The bias reduction method proposed by Tong et al. (2019) has demonstrated its efficacy in reducing the effects of bias on the estimation of association parameters between genotype and phenotype while minimizing variance by employing chart reviews on a subset of the data for validating phenotypes, however its improvement of subsequent PRS prediction accuracy remains unclear.

Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.

Introduction: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts.

Methods: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses.

A single dose for me, A wealth of protection for us: The public health cost of individualism in the rollout of COVID-19 vaccine.

Objective: This study examines whether individualism weakens the effectiveness of the COVID-19 vaccine eligibility expansions in the United States in 2021, and assesses the associated social benefits or costs associated with individualism.

Methods: We construct a county-level composite individualism index as a proxy of culture and the fraction of vaccine eligible population as a proxy of vaccination campaign (mean: 41.34%).

MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons.

Inclusions comprised of microtubule-associated protein tau (tau) are implicated in a group of neurodegenerative diseases, collectively known as tauopathies, that include Alzheimer's disease (AD). The spreading of misfolded tau "seeds" along neuronal networks is thought to play a crucial role in the progression of tau pathology. Consequently, restricting the release or uptake of tau seeds may inhibit the spread of tau pathology and potentially halt the advancement of the disease.

Association of Structural Forms of 17q21.31 with the Risk of Progressive Supranuclear Palsy and Sub-haplotypes.

Importance: The chromosome 17q21.31 region, containing a 900 Kb inversion that defines H1 and H2 haplotypes, represents the strongest genetic risk locus in progressive supranuclear palsy (PSP). In addition to H1 and H2, various structural forms of 17q21.

A comparative study of structural variant calling in WGS from Alzheimer's disease families.

Detecting structural variants (SVs) in whole-genome sequencing poses significant challenges. We present a protocol for variant calling, merging, genotyping, sensitivity analysis, and laboratory validation for generating a high-quality SV call set in whole-genome sequencing from the Alzheimer's Disease Sequencing Project comprising 578 individuals from 111 families. Employing two complementary pipelines, Scalpel and Parliament, for SV/indel calling, we assessed sensitivity through sample replicates (N = 9) with in silico variant spike-ins.

Region-based analysis with functional annotation identifies genes associated with cognitive function in South Asians from India.

The prevalence of dementia among South Asians across India is approximately 7.4% in those 60 years and older, yet little is known about genetic risk factors for dementia in this population. Most known risk loci for Alzheimer's disease (AD) have been identified from studies conducted in European Ancestry (EA) but are unknown in South Asians.

LUSTR: a new customizable tool for calling genome-wide germline and somatic short tandem repeat variants.

Background: Short tandem repeats (STRs) are widely distributed across the human genome and are associated with numerous neurological disorders. However, the extent that STRs contribute to disease is likely under-estimated because of the challenges calling these variants in short read next generation sequencing data. Several computational tools have been developed for STR variant calling, but none fully address all of the complexities associated with this variant class.

Human whole-exome genotype data for Alzheimer's disease.

The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to a joint analysis. Here we present a bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen sequencing centers in the Alzheimer's Disease Sequencing Project. The joint-genotype called variant-called format (VCF) file contains only positions within the union of capture kits.