In just over a decade, advances in genome-wide association studies (GWAS) have offered an approach to stratify individuals based on genetic risk for disease. Using recent Alzheimer's disease (AD) GWAS results as the base data, we determined each individual's polygenic risk score (PRS) in the UK Biobank dataset. Using individuals within the extreme risk distribution, we performed a GWAS that is agnostic of AD phenotype and is instead based on known genetic risk for disease. To interpret the functions of the new risk factors, we conducted phenotype analyses, including a phenome-wide association study. We identified 246 loci surpassing the significance threshold of which 229 were not reported in the base AD GWAS. These include loci that showed suggestive levels of association in the base GWAS and loci not previously suspected to be associated with AD. Among these, there are loci, such as IL34 and KANSL1, that have since been shown to be associated with AD in recent studies. We also show highly significant genetic correlations with multiple health-related outcomes that provide insights into prodromal symptoms and comorbidities. This is the first study to utilize PRS as a phenotype-agnostic group classification in AD genetic studies. We identify potential new loci for AD and detail phenotypic analysis of these PRS extremes.

Anthropogenic noise is a ubiquitous feature of the American landscape, and is a known stressor for many bird species, leading to negative effects in behavior, physiology, reproduction, and ultimately fitness. While a number of studies have examined how anthropogenic noise affects avian fitness, there are few that simultaneously examine how anthropogenic noise impacts the relationship between parental care behavior and nestling fitness. We conducted Brownian noise playbacks for 6 h a day during the nesting cycle on Eastern Bluebird (Sialia sialis) nest boxes to investigate if experimentally elevated noise affected parental care behavior, nestling body conditions, and nestling stress indices. We documented nest attendance by adult females using radio frequency identification (RFID), and we assessed nestling stress by measuring baseline corticosterone levels and telomere lengths. Based on the RFID data collected during individual brood cycles, adult bluebirds exposed to noise had significantly higher feeding rates earlier in the brood cycle than adults in the control group, but reduced feeding rates later in the cycle. Nestlings exposed to noise had higher body conditions than the control nestlings at 11 days of age, but conditions equalized between treatments by day 14. We found no differences in nestling baseline corticosterone levels or nestling telomere lengths between the two treatment groups. Our results revealed that noise altered adult behavior, which corresponded with altered nestling body condition. However, the absence of indicators of longer-term effects of noise on offspring suggests adult behavior may have been a short-term response.