03011nas a2200361 4500008004100000022001400041245015500055210006900210260001600279520191700295100002202212700001702234700001702251700002302268700002102291700001602312700002002328700002202348700002102370700001902391700001402410700002102424700001802445700002002463700001902483700002202502700001802524700001902542700001602561700001902577700001702596856003602613 2019 eng d a1550-910900aEpigenome-wide association analysis of daytime sleepiness in the Multi-Ethnic Study of Atherosclerosis reveals African-American-specific associations.0 aEpigenomewide association analysis of daytime sleepiness in the  c2019 May 293 a

STUDY OBJECTIVES: Daytime sleepiness is a consequence of inadequate sleep, sleep-wake control disorder, or other medical conditions. Population variability in prevalence of daytime sleepiness is likely due to genetic and biological factors as well as social and environmental influences. DNA methylation (DNAm) potentially influences multiple health outcomes. Here, we explored the association between DNAm and daytime sleepiness quantified by the Epworth Sleepiness Scale (ESS).

METHODS: We performed multi-ethnic and ethnic-specific epigenome-wide association studies for DNAm and ESS in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 619) and the Cardiovascular Health Study (n = 483), with cross-study replication and meta-analysis. Genetic variants near ESS-associated DNAm were analyzed for methylation quantitative trait loci and followed with replication of genotype-sleepiness associations in the UK Biobank.

RESULTS: In MESA only, we detected four DNAm-ESS associations: one across all race/ethnic groups; three in African-Americans (AA) only. Two of the MESA AA associations, in genes KCTD5 and RXRA, nominally replicated in CHS (p-value < 0.05). In the AA meta-analysis, we detected 14 DNAm-ESS associations (FDR q-value < 0.05, top association p-value = 4.26 × 10-8). Three DNAm sites mapped to genes (CPLX3, GFAP, and C7orf50) with biological relevance. We also found evidence for associations with DNAm sites in RAI1, a gene associated with sleep and circadian phenotypes. UK Biobank follow-up analyses detected SNPs in RAI1, RXRA, and CPLX3 with nominal sleepiness associations.

CONCLUSIONS: We identified methylation sites in multiple genes possibly implicated in daytime sleepiness. Most significant DNAm-ESS associations were specific to AA. Future work is needed to identify mechanisms driving ancestry-specific methylation effects.

1 aBarfield, Richard1 aWang, Heming1 aLiu, Yongmei1 aBrody, Jennifer, A1 aSwenson, Brenton1 aLi, Ruitong1 aBartz, Traci, M1 aSotoodehnia, Nona1 aChen, Yii-der, I1 aCade, Brian, E1 aChen, Han1 aPatel, Sanjay, R1 aZhu, Xiaofeng1 aGharib, Sina, A1 aJohnson, Craig1 aRotter, Jerome, I1 aSaxena, Richa1 aPurcell, Shaun1 aLin, Xihong1 aRedline, Susan1 aSofer, Tamar uhttps://chs-nhlbi.org/node/8096