Common Genetic Variants in ARNTL and NPAS2 and at Chromosome 12p13 are Associated with Objectively Measured Sleep Traits in the Elderly

Evans DS, Parimi N, Nievergelt CM, Blackwell T, Redline S, Ancoli-Israel S, Orwoll ES, Cummings SR, Stone KL, Tranah GJ; Study of Osteoporotic Fractures (SOF); Osteoporotic Fractures in Men (MrOS) Study Group. Sleep. 2013 Mar 1;36(3):431-46

To determine the association between SNPs in circadian genes and sleep disturbances in the elderly, data was analyzed from 2 different cohort studies; the Study of Osteoporotic Fractures (SOF) and Osteoporotic Fractures in Men (MrOS). Participants were aged 65 or older, were genotyped and had their activity measured via wrist-mounted actigraphs.

It was determined that several SNPs were associated with many characteristics of sleep. In a meta analysis of both studies, rs1047776 in leprel2 and rs2238114 in usp5 are associated with wake after sleep onset, a measure of sleep quality. In the MrOS study, rs3816358 in bmal1, rs3768984 in npas2, and their interaction were found to be associated with sleep and wake timing. Finally, the SOF analysis found that rs895520 in npas2 and rs1047776 in leprel2 were associated with activity robustness and sleep latency respectively.

rs1047776 in leprel2

Leprel2 rs1047776

NCBI Variation Viewer rs1047776

rs2238114 in usp5

usp5 rs2238114

NCBI Variation Viewer rs2238114

rs3816358 in bmal1

bmal1 rs3816358

NCBI Variation Viewer rs3816358

rs3768984 and rs895520 in npas2

npas2 rs3768984-rs895520

NCBI Variation Viewer rs3768984-rs895520


Two new rare variants in the circadian “clock” gene may influence sleep pattern

Pirovano A, Lorenzi C, Serretti A, Ploia C, Landoni S, Catalano M, Smeraldi E and Lorenzi C. Genetics in Medicine. 2005;7: 455–457.

To confirm the role of clock SNPs in mood disorders, an Italian study was performed, and a rare clock gene SNP was found to only be present in those with mood disorders. None of the 76 healthy controls and 2 of the 1037 ill patients had this rare mutation.

These patients both had disturbed sleep schedules and difficulty maintaining consistent daily rhythms. However, a statistical analysis was not performed to estimate the size of the mutation’s effect or to determine whether the results were simply due to variability.