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.


REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American

Garaulet M, Smith CE, Gomez-Abellán P, Ordovás-Montañés M, Lee YC, Parnell LD, Arnett DK, Ordovás JM. Mol Nutr Food Res. 2014 Apr;58(4):821-9.

To determine the role of SNPs in metabolic disease, a study of 810 North American and 1404 Spanish Mediterranean subjects was performed. Subjects had blood, anthropometrics, dietary intake (via Diet History Questionnaire) and physical activity (via International Physical Activity Questionnaire) assessed to determine metabolic status. 

The authors found that carriers of the minor alleles of a SNP (rs2314339) in rev-erb-α were less likely to be obese, had more daily and weekly physical activity, and lower waist circumference. The study also investigated the association between the SNP and diet, but no significant findings were replicated in both populations

rs2314339 in rev-erb-α

reverba rs2314339

NCBI Variation Viewer rs2314339

Association of circadian genes with diurnal blood pressure changes and non-dipper essential hypertension: a genetic association with young-onset hypertension

Leu HB, Chung CM, Lin SJ, Chiang KM, Yang HC, Ho HY, Ting CT, Lin TH, Sheu SH, Tsai WC, Chen JH, Yin WH, Chiu TY, Chen CI, Fann CS, Chen YT, Pan WH, Chen JW. Hypertens Res. 2015 Feb;38(2):155-62.

To establish the relationship between circadian rhythms and cardiovascular health, a study of 372 young hypertensives was performed, in which SNPs in the circadian genes bmal1 (rs3816358), per2 (rs6431590), npas2 (rs3888170), ror (rs10519096) and β (rs1410225) were shown to be predictive of non-dipping hypertension (as measured via ambulatory blood pressure). A second cohort of 619 young-onset hypertensives were then assessed, and confirmed the genetic association.

The SNPs are found in:


bmal1 rs3816358

NCBI Variation Viewer rs3816358


per2 rs6431590

NCBI Variation Viewer rs6431590


 npas2 rs3888170

NCBI Variation Viewer rs3888170


ror-a rs10519096

NCBI Variation Viewer rs10519096


ror-b rs1410225

NCBI Variation Viewer rs1410225

CRY2 Is Associated with Depression

Lavebratt C, Sjöholm LK, Soronen P, Paunio T, Vawter MP, Bunney WE, Adolfsson R, Forsell Y, Wu JC, Kelsoe JR, Partonen T, Schalling M. PLoS One. 2010 Feb 24;5(2):e9407.

To determine the role of cry2 in bipolar disorder, winter depression and sleep deprivation, the authors performed two separate studies in Swedes and Finns.

First, they subjected patients with bipolar disorder (n=13, diagnosed according to DSM-IV criteria) and (n=8) healthy controls to sleep deprivation, and found that cry2 gene expression was increased only in healthy individuals.

Next, they recruited and genotyped bipolar patients from psyciatric specialists and matched controls from the general population. They found that in both the Finnish (n=1182) and Swedish (n=1129) samples, those with seasonal affective disorder were more likely to have risk alleles for SNPs (rs10838524A-rs10838527G-rs3824872A) in the cry2 gene.

The SNPs in cry2

cry2 rs10838524-rs10838527-rs3824872

NCBI Variation Viewer rs10838524-rs10838527-rs3824872