Biology subjects

Yaffe, K.

Publications and source records attributed to Yaffe, K..

3 recordsLinked to original sources

bioRxiv2023

Multivariate prediction of cognitive performance from the sleep electroencephalogram

Human cognitive performance is a key function whose biological foundations have been partially revealed by genetic and brain imaging studies. The sleep electroencephalogram (EEG) is tightly linked to structural and functional features of the central nervous system and serves as another promising biomarker. We used data from MrOS, a large cohort of older men and cross- validated regularized regression to link sleep EEG features to cognitive performance in cross- sectional analyses. In independent validation samples 2.5-10% of variance in cognitive performance can be accounted for by sleep EEG features, depending on the covariates used. Demographic characteristics accounted for more covariance between sleep EEG and cognition than health variables, and consequently reduced this association by a greater degree, but even with the strictest covariate sets a statistically significant association was present. Sigma power in NREM and beta power in REM sleep were associated with better cognitive performance, while theta power in REM sleep was associated with worse performance, with no substantial effect of coherence and other sleep EEG metrics. Our findings show that cognitive performance is associated with the sleep EEG (r=0.283), with the strongest effect ascribed to spindle- frequency activity. This association becomes weaker after adjusting for demographic (r=0.186) and health variables (r=0.155), but its resilience to covariate inclusion suggest that it also partially reflects trait-like differences in cognitive ability.

neuroscience↗

bioRxiv2019

Genetic risk score for Alzheimer's disease is associated with poor hearing

IntroductionIncipient dementia or shared genetics may partly explain the association between hearing loss and dementia. We evaluated whether genetic variants known to increase Alzheimers disease (AD) also influence hearing difficulty. MethodsUK Biobank participants aged 56+ with Caucasian genetic ancestry self-reported difficulty hearing and hearing with background noise (n=244,915) and underwent objectively measured hearing assessments (n=80,074). Poor objective hearing was defined as >-5.5 dB speech reception threshold on a Digit Triplet Test. We evaluated whether an AD genetic risk score (AD-GRS; range -1.2 to 1.9), the weighted sum of 23 previously identified AD-related polymorphisms, predicted objective or self-reported poor hearing, using age, sex, and genetic ancestry adjusted logistic regression models. ResultsHigher AD-GRS predicted objectively measured poor hearing (OR=1.06; 95% CI: 1.01, 1.11) and self-reported problems hearing with background noise (OR=1.03; 95% CI: 1.00, 1.05). DiscussionUsing novel methods, we found evidence that AD genetic risk influences hearing loss.

epidemiology↗

bioRxiv2018

Lipid associated polygenic enrichment in Alzheimer’s disease

Cardiovascular (CV) and lifestyle associated risk factors (RFs) are increasingly recognized as important for Alzheimers disease (AD) pathogenesis. Beyond the [isin]4 allele of apolipoprotein E (APOE), comparatively little is known about whether CV associated genes also increase risk for AD (genetic pleiotropy). Using large genome-wide association studies (GWASs) (total n > 500,000 cases and controls) and validated tools to quantify genetic pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with AD and one or more CV RFs, namely body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD), waist hip ratio (WHR), total cholesterol (TC), low-density (LDL) and high-density lipoprotein (HDL). In fold enrichment plots, we observed robust genetic enrichment in AD as a function of plasma lipids (TC, LDL, and HDL); we found minimal AD genetic enrichment conditional on BMI, T2D, CAD, and WHR. Beyond APOE, at conjunction FDR < 0.05 we identified 57 SNPs on 19 different chromosomes that were jointly associated with AD and CV outcomes including APOA4, ABCA1, ABCG5, LIPG, and MTCH2/SPI1. We found that common genetic variants influencing AD are associated with multiple CV RFs, at times with a different directionality of effect. Expression of these AD/CV pleiotropic genes was enriched for lipid metabolism processes, over-represented within astrocytes and vascular structures, highly co-expressed, and differentially altered within AD brains. Beyond APOE, we show that the polygenic component of AD is enriched for lipid associated RFs. Rather than a single causal link between genetic loci, RF and the outcome, we found that common genetic variants influencing AD are associated with multiple CV RFs. Our collective findings suggest that a network of genes involved in lipid biology also influence Alzheimers risk.

genetics↗