We further examined the genes within genome-wide significant loci using gene-based pathway and tissue enrichment analyses45 (link),47 (link),69 (link). Gene-based analysis was performed using PASCAL, which estimated a combined association P value from the summary statistics of multiple SNPs in a gene45 (link). Pathway and ontology enrichment analyses were performed using FUMA69 (link) and EnrichR47 (link). Tissue enrichment analysis was performed using MAGMA46 (link) in FUMA, which controlled for gene size. Pathway and tissue enrichment analyses were also performed on genes within loci belonging to sleep propensity and sleep fragmentation clusters separately.
We constructed a weighted GRS comprising the 42 significant sleepiness loci and tested for associations with other self-reported sleep traits (sleep duration, long sleep duration, short sleep duration, insomnia, chronotype, and day naps), and 7-day accelerometry traits in the UK Biobank. Weighted GRS analyses were performed by summing the products or risk allele count multiplied by the effect estimate reported in the primary GWAS of self-reported daytime sleepiness using R package gds (https://cran.r-project.org/web/packages/gds/gds.pdf ). We also tested the GRSs of reported loci for insomnia, sleep duration, short sleep, long sleep, day naps, chronotype, restless legs syndrome (RLS), narcolepsy, and coffee consumption associated with self-reported daytime sleepiness using the same approach. The SNPs selected for each trait include 57 genome-wide significant loci for frequent insomnia49 (link); 78, 27, and 8 loci for sleep duration, long sleep, and short sleep, respectively59 (link); 348 loci for chronotype67 (link); 125 loci for daytime napping; 20 genome-wide significant loci for RLS48 (link); 8 non-HLA suggestive significant loci (P < 10−4) in a narcolepsy case–control study of European Americans51 , and 8 loci for coffee consumption50 (link).
We constructed a weighted GRS comprising the 42 significant sleepiness loci and tested for associations with other self-reported sleep traits (sleep duration, long sleep duration, short sleep duration, insomnia, chronotype, and day naps), and 7-day accelerometry traits in the UK Biobank. Weighted GRS analyses were performed by summing the products or risk allele count multiplied by the effect estimate reported in the primary GWAS of self-reported daytime sleepiness using R package gds (
Full text: Click here