NEW YORK (GenomeWeb) – A team of 23andMe researchers has conducted a genome-wide association study tying certain genetic variants to being a morning person.
The researchers drew upon information from some 89,000 23andMe customers whom they queried about their propensity to get up early or sleep in the morning. As they reported today in Nature Communications, they linked 15 loci, about half of which are located near known circadian rhythm genes, to the morning versus. evening preference. They also explored whether being a morning person was associated with other phenotypes like insomnia, BMI, and depression.
"In this study we set out to discover more about an individual's preference toward early rising and were able to identify the genetic associations with 'morningness' as well as ties to lifestyle patterns and other traits," first author Youna Hu from 23andMe said in a statement.
Hu and her colleagues analyzed the genetic associations of being a morning person — as determined through two web-based survey questions — in a cohort of 89,283 customers who'd agreed to participate in research studies. Of the people who answered the survey, about three-quarters could be scored based on their answers as either a morning or a night person. Neutral or discordant responses were discarded.
Women, they noted, were more likely to be morning people than men, and preference for the morning increased with age. Further, morning people were less likely to report insomnia, needing more than eight hours of sleep a night, or restless leg syndrome. They also have a lower prevalence of depression and of being underweight or obese.
For their genetic analyses, the researchers focused on individuals of European ancestry, removing any related people, and examined their genomes at some 8 million genotyped or imputed sites.
Through this, Hu and her colleagues linked seven loci near established circadian rhythm genes to morningness. For instance, they reported that rs12736689 is in strong linkage disequilibrium with the H137R variant of the nearby RGS16 gene. RGS16 is a G protein-signaling regulator, and mice lacking this gene have a longer circadian period, the researchers noted.
Likewise, they linked rs9479402, which is 54 kilobases upstream of VIP, to morningness. VIP is a key neuropeptide in the suprachiasmatic nucleus (SCN) of the hypothalamus, and the SCN is made up of cellular oscillators that respond to light perceived by the retina.
They also found that loci near other circadian rhythm genes of PER2, HCRTR2, RAD1, PER3, and CLN5 were also associated with being a morning person.
The researchers also uncovered associations with four genes — PLCL1, APH1A, FBXL13, and NOL4 — with potential circadian roles, as determined through a literature review.
Through a pathway analysis using the computational tool MAGENTA, Hu and her colleagues found that their GWAS was enriched for circadian rhythm or clock pathways. They noted that the top three pathways are indeed circadian related and even share another four genes: PER2, ARNTL, CRY1, and CRY2.
Hu and her colleagues also examined whether being a morning person was linked to sleep and other phenotypes. After adjusting for age, gender, and ancestry, they found that the odds of a morning person suffering from insomnia is 55 percent that of night owls, and the odds of morning person having sleep apnea is 64 percent that of night people.
However, they were unable to find clear genetic associations with related sleep phenotypes like insomnia, sleep apnea, and sleeping soundly. The researchers suggested that these phenotypes might be heterogeneous, influenced by environmental factors, or more subject to self-reporting bias.
Similarly, the odds of a morning person reporting depression is 61 percent that of night owls, and the average BMI of a morning person is 0.99kgm-2 lower. Using a Mendelian randomization approach, they found no evidence that being a morning person was protective of depression or high BMI. But by going back to the GWAS results, they found that a variant of the BMI-linked FTO gene has some evidence for association with morningness, suggesting an association to be further explored, they said.