Table 1.
SNPs in circadian rhythm-related genes associated with metabolic dysfunction, obesity and T2DM in humans.
| Gene and location | SNP [allele(s)] | Study Population | Association | Reference |
|---|---|---|---|---|
| Clock (4q12) | rs1554483 (G) rs4580704 (C) rs68437222 (C) rs6850524 (G) rs4864548 (A) rs1554483-rs4864548 (GA) |
Lean (n=715) and overweight/obese (n=391) individuals of self-reported European descent in Buenos Aires, Argentina. | Up to 1.8-fold risk of developing overweight/obesity | (115) |
| rs4580704 (CC) rs1801260 (C) |
1100 American individuals of European descent | Increased risk of developing metabolic syndrome components | (116) | |
| rs4864548-rs3736544-rs1801260 (CAT) | 537 individuals from 89 British families (all white European) | Associated with presence of metabolic syndrome | (117) | |
| rs4580704 (CC) | 7098 individuals with T2DM or with 3 or more cardiovascular risk factors (all European) | Increased fasting glucose, and increased development of T2DM. Increased risk of cardiovascular disease in individuals with T2DM. | (118) | |
| Npas2 (2q11) | rs11541353 (C) | 517 Finnish individuals | Associated with hypertension | (119) |
| Bmal1 (11p15) | rs7950226-rs11022775 (haplotype AC) | 1304 individuals from 424 British families with T2DM of European descent | T2DM | (120) |
| rs6486121-rs3789327- rs969485 (CCA) | Hypertension | |||
| rs7950226 (A) rs11022775 (C) rs7950226-rs11022775 (GC) rs7950226-rs11022775 (AC) |
185 women with Gestational diabetes and 161 controls (Greek population) | Increased risk of developing gestational diabetes | (121) | |
| Cry2 (11p11) | rs11605924 (A) | 21 GWAS cohorts including up to 46,186 non-diabetic individuals, with a further follow up of 25 loci in 76,558 additional individuals of white European descent from United States or Europe | Higher fasting glucose levels | (122) |
| Per2 (2q37) | 10870 (A) | 517 Finnish individuals | Increased risk of raised plasma glucose | (119) |
| rs2304672 (G) rs4663302 (T) |
454 overweight/obese Spanish individuals | Increased snacking, higher stress when dieting, more likely to eat when bored Higher waist circumference and waist to hip ratio |
(123) | |
| Mtnr1b (11q14) | rs1387153 (T) | 2151 non-diabetic (encompassing lean and obese) French subjects with European ancestry. Replication analysis conducted in 5,518 middle-aged non-diabetic Danish individuals, 3,886 and 1,453 non-diabetic French individuals from 2 cohorts and 5,237 young (16 years of age) Finnish individuals | Increased fasting blood glucose, increased risk of developing hyperglycemia and T2DM | (124) |
| rs10830963 (G) | 10 GWAS study cohorts and 13 case-control studies (18,236 cases, 64,453 controls) of European descent | Increased fasting blood glucose levels, reduced beta cell functions and an increased risk of developing T2DM | (125) |