Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease.

Almost every recent Alzheimer's disease (AD) genome-wide association study (GWAS) has performed meta-analysis to combine studies with clinical diagnosis of AD with studies that use proxy phenotypes based on parental disease history. Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and nonrandom participation in parental illness surveys, which cause substantial discrepancies between AD GWAS and GWAX results. We demonstrate that the current AD GWAX provide highly misleading genetic correlations between AD risk and higher education, which subsequently affects a variety of genetic epidemiological applications involving AD and cognition.

Optimizing and benchmarking polygenic risk scores with GWAS summary statistics.

Background: Polygenic risk score (PRS) is a major research topic in human genetics. However, a significant gap exists between PRS methodology and applications in practice due to often unavailable individual-level data for various PRS tasks including model fine-tuning, benchmarking, and ensemble learning.

Results: We introduce an innovative statistical framework to optimize and benchmark PRS models using summary statistics of genome-wide association studies.

Valid inference for machine learning-assisted genome-wide association studies.

Machine learning (ML) has become increasingly popular in almost all scientific disciplines, including human genetics. Owing to challenges related to sample collection and precise phenotyping, ML-assisted genome-wide association study (GWAS), which uses sophisticated ML techniques to impute phenotypes and then performs GWAS on the imputed outcomes, have become increasingly common in complex trait genetics research. However, the validity of ML-assisted GWAS associations has not been carefully evaluated.

Mid-to-Late Life Healthy Lifestyle Modifies Genetic Risk for Longitudinal Cognitive Aging among Asymptomatic Individuals.

Importance: Genetic and lifestyle factors contribute to an individual's risk of developing Alzheimer's disease. However, it is unknown whether and how adherence to healthy lifestyles can mitigate the genetic risk of Alzheimer's.

Objective: The aim of this study is to investigate whether adherence to healthy lifestyles can modify the impact of genetic predisposition to Alzheimer's disease on later-life cognitive decline.

The Big (Genetic) Sort? A Research Note on Migration Patterns and Their Genetic Imprint in the United Kingdom.

This research note reinvestigates Abdellaoui et al.'s (2019) findings that genetically selective migration may lead to persistent and accumulating socioeconomic and health inequalities between types (coal mining or non-coal mining) of places in the United Kingdom. Their migration measure classified migrants who moved to the same type of place (coal mining to coal mining or non-coal mining to non-coal mining) into "stay" categories, preventing them from distinguishing migrants from nonmigrants.

Pervasive biases in proxy GWAS based on parental history of Alzheimer's disease.

Almost every recent Alzheimer's disease (AD) genome-wide association study (GWAS) has performed meta-analysis to combine studies with clinical diagnosis of AD with studies that use proxy phenotypes based on parental disease history. Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and non-random participation of parental illness survey, which cause substantial discrepancies between AD GWAS and GWAX results. We demonstrate that current AD GWAX provide highly misleading genetic correlations between AD risk and higher education which subsequently affects a variety of genetic epidemiologic applications involving AD and cognition.

Apolipoprotein E moderates the association between non-APOE polygenic risk score for Alzheimer's disease and aging on preclinical cognitive function.

Introduction: Variation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (eg, a non-APOE polygenic risk score [PRS]) may interact with the APOE ε4 allele to influence cognitive decline.

Methods: We tested the PRS × APOE ε4 × age interaction on preclinical cognition using longitudinal data from the Wisconsin Registry for Alzheimer's Prevention. All analyses were fitted using a linear mixed-effects model and adjusted for within individual/family correlation among 1190 individuals.

Apolipoprotein E moderates the association between Non- Polygenic Risk Score for Alzheimer's Disease and Aging on Preclinical Cognitive Function.

Introduction: Variation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (e.g., a non- polygenic risk scores [PRS]) may interact with the ε4 allele to influence cognitive decline.

Detecting genetic heterogeneities in response to trauma: The case of 9/11.

The current study evaluates genetic heterogeneities in response to trauma among U.S. young adults.

Higher educational attainment is associated with longer telomeres in midlife: Evidence from sibling comparisons in the UK Biobank.

Prior studies have established that higher educational attainment is associated with a longer telomere length (TL), a marker of cellular aging. However, it is unclear whether extant associations are causal, since they are likely confounded by unobserved genetic, early-life and family background factors that are correlated with education and TL. We leverage sibling differences in TL, education and measured genetics (polygenic scores for educational attainment and TL) to estimate associations between educational attainment and TL in midlife for European ancestry individuals in the UK Biobank, while controlling for unobserved confounders shared by siblings.

Effects of a dammarane-type saponin, ginsenoside Rd, in nicotine-induced vascular endothelial injury.

Background: Panax notoginseng (Burk.) F.H.