Rs10766071

Rs10766071 is a SNP in aryl hydrocarbon receptor nuclear translocator-like (ARNTL). Rs10766071 has been associated with shorter sleep duration as measured by polysomnography— a method for recording the activity of the brain, eyes, muscles, and heart while the subject sleeps. The A allele (major allele) is associated with higher sleep duration and the G allele (minor allele) is associated with shorter sleep duration (n=414). However, only one individual with the GG genotype was in the study. G is the ancestral allele and is also the minor variant (frequency = .0851) (dbSNP).

ARNTL encodes a basic helix-loop-helix (bHLH) PAS domain transcription factor (PMID:11163178).Studies have shown that ARNTL is an important component of the transcriptional-translational feedback loop (TTFL) which regulates circadian rhythms. Homozygous ARNTL null mutant mice loose circadian rhythmicity, as measured by activity patterns, when transferred to constant darkness, demonstrating that ARNTL plays a key role in maintaining circadian rhythmicity (PMID:11163178).

Rs1076671 was one of 13 significant SNPs (after Bonferroni correction) discovered by Kripke et al. (PMID:25660813) to be associated with sleep variables. Their study consisted of a cohort of patients of likely European ancestry who were recruited from a “busy academic sleep practice.” Patients consisted mostly of individuals who had been given a tentative diagnosis of sleep apnea, and had been sent for a polysomnography to confirm. All patients were 21 years or older.The authors of the paper collected DNA samples from the patients and then performed custom Illumina golden gate assay for 768 single nucleotide polymorphisms. This subset of SNPs was chosen because they were relevant to circadian rhythm regulation. Patients were surveyed about their sleep schedule and habits and polysomnographs were recorded of each patient. Thirty-eight phenotypic measures were analyzed. The authors performed linear or logistic regression analyses and then performed a Bonferroni correction for the total number of SNPs tested. The p-value for this association was 5.3x10-5 prior to Bonferroni correction. Importantly, this SNP is not genome-wide significant.

References:

Database of Single Nucleotide Polymorphisms (dbSNP). Bethesda (MD): National Center for Biotechnology Information, National Library of Medicine. dbSNP accession: rs10766071 (dbSNP Build ID: 120/142). Available from: http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=10766071

PMID: 25660813: Kripke, Daniel F., et al. "Genetic variants associated with sleep disorders." Sleep Medicine (2014).

PMID:11163178: Bunger, Maureen K., et al. "Mop3 is an essential component of the master circadian pacemaker in mammals." Cell 103.7 (2000): 1009-1017.