Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire n...
Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide crit...
The Austronesian dispersal across the Indonesian Ocean to Madagascar and the Comoros has been well documented, but in an unexplained anomaly, few to no traces have been found of the Austronesian expansion in East Africa or the Arabian Peninsula. To revisit this peculiarity, we surveyed the Western Indian Ocean rim populations to identify potential Austronesian genetic ancestry. We generated full mitochondrial D...
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common varian...