- Goodman, Matthew O;
- Faquih, Tariq;
- Paz, Valentina;
- Nagarajan, Pavithra;
- Lane, Jacqueline M;
- Spitzer, Brian;
- Maher, Matthew;
- Chung, Joon;
- Cade, Brian E;
- Purcell, Shaun M;
- Zhu, Xiaofeng;
- Noordam, Raymond;
- Phillips, Andrew JK;
- Kyle, Simon D;
- Spiegelhalder, Kai;
- Weedon, Michael N;
- Lawlor, Deborah A;
- Rotter, Jerome I;
- Taylor, Kent D;
- Isasi, Carmen R;
- Sofer, Tamar;
- Dashti, Hassan S;
- Rutter, Martin K;
- Redline, Susan;
- Saxena, Richa;
- Wang, Heming
Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p < 8.3e-9), along with 341 previously reported loci (p < 5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2 = 0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post-GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections (including potential causal links) to behavioral, psychological, and cardiometabolic traits.