Table 1.
A summary of genetic variants in clock components and their associations with chronotypes, eating behaviours and health parameters.
| Genetic Variant/Haplotypes | Population | Observations | Ref |
|---|---|---|---|
| CLOCK rs1801260 | 421 Japanese subjects | C allele associated with an evening chronotype with significant delayed onset of sleep, shorter sleep times, greater daytime sleepiness | [52] |
| 500 overweight and obese subjects during 28-week weight-loss program | C allele carriers more emotional eaters and more resistant to weight loss | [53] | |
| 284, 92 controls vs. 192 overweight and obese with or without binge eating disorder | C allele predisposes obese individuals to a higher BMI | [54] | |
| 1272 overweight and obese participants attending 30-week weight-loss program | C allele carriers were emotional eaters and lost less weight and at a lower rate compared to non-emotional eaters with the same risk allele or non-risk allele | [55] | |
| 370 children aged 6–13 years | No association between the genotype and sleep duration. However, there seems to be a trend between sleep duration and overweight | [56] | |
| 85 overweight women | C allele carriers with significant circadian abnormalities: lower amplitude and greater fragmentation of the rhythm, and an evening chronotype | [57] | |
| 1495 overweight/obese subjects participating in a Mediterranean-diet-based weight-reduction program for 28 weeks | C allele carriers are more resistant to weight loss, shorter sleep duration, higher plasma ghrelin concentrations, delayed breakfast time, evening preference and less compliance with a Mediterranean diet plan | [58] | |
| 475 metabolic syndrome subjects participating in the CORDIOPREV clinical trial for 1 year | Gene diet interactions; C carriers showed non-significant improved insulin sensitivity while T carriers have significantly improved insulin sensitivity on low-fat diet | [59] | |
| CLOCK haplotype rs1554483 and rs4864548 | 715 lean and 391 overweight or obese | GA haplotype associated with a 1.8-fold risk of overweight or obesity | [60] |
| CLOCK rs3749474 | 500 overweight/obese subjects | T allele carriers have significantly higher weight, BMI and waist circumference | [53] |
| CLOCK rs3749474 | 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) | T allele carriers have significantly higher energy, total fat, protein and carbohydrate intakes | [61] |
| CLOCK rs3749474 | 898 subjects | T allele associated positively with higher BMI and evening carbohydrate intake | [62] |
| CLOCK rs6850524 | 260 cases with abdominal obesity and 260 controls Chinese population | CC genotype have a lower risk of overweight or obesity than those with GG genotype | [63] |
| CLOCK haplotype rs4864548-rs3736544-rs1801260 | 537 individuals from 89 families characterized for inflammatory, atherothrombotic and metabolic risk associated with insulin resistance. | CGC haplotype protective for the development of obesity and the CAT haplotype is associated with the presence of the metabolic syndrome | [64] |
| CLOCK rs4580704 | 7098 PREvención con DIeta MEditerránea (PREDIMED) trial over a median duration of 4.8 years | G allele with decreased incidence of type 2 diabetes and associated stroke. Mediterranean diet provides further protection in G allele carriers. | [65] |
| 897 patients from the CORDIOPREV clinical trial, low-fat diet and Mediterranean diet for 12 months | C allele carriers showed significant reduction in CRP levels and an improvement in HDL/ApoA1 ratio after a low-fat diet for 12 months | [66] | |
| 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) | G allele show lower blood pressure and higher erythrocyte membrane oleic acid (MUFA) and improved insulin sensitivity in high-MUFA intake | [67] | |
| CLOCK haplotype rs3749474-rs4580704-rs1801260 | 1100 individual participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) | The haplotype CGA was associated with lower BMI, weight, waist circumference, adiponectin concentration, blood pressure and with oleic acid (MUFA) RBC membrane composition. | [67] |
| CLOCK rs12649507, rs6858749 | 14,906 from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium | Longer habitual sleep duration is associated with lower BMI and a favourable dietary behaviour. rs12649507 G allele: Higher PUFA intake and more sleep.rs6858749 T allele: Lower protein intake with each additional hour of sleep | [68] |
| CLOCK rs10002541 and rrs6850524 | 260 cases with abdominal obesity and 260 controls, Chinese population | Significant associations between CG and TG haplotypes and abdominal obesity. rs10002541 C allele is protective for abdominal obesity. | [63] |
| CLOCK rs12649507 and rs11932595 | 1011 individuals from Tyrol and Estonia | The haplotype GGGG in Tyrolean and GGAA in Estonian population associated with longer sleep | [69] |
| CLOCK rs1801260 BMAL1 rs2278749 | 507 healthy young adults | CLOCK rs1801260 associated with seasonal affective disorder and it synergistically interacts with BMAL1 rs2278749. Seasonal variation in body weight and appetite also associated with BMAL1 rs2278749. | [70] |
| CLOCK rs1801260 + SIRT1 rs1467568 | 1465 Overweight/obese subjects over 30 weeks of Mediterranean-diet-based weight-loss program | SIRT1 (A allele) ad CLOCK (C allele) are more resistant to lose weight and have more of an evening preference | [71] |
| PER2 gene rs4663302 rs2304672 | 454 obese subjects, weight reduction program based on Mediterranean diet | PER2 gene rs4663302 rs2304672 associated with abdominal obesity. rs4663302 T allele and rs2304672 G allele carriers associated with not completing the weight-loss programme. rs2304672 G also linked to extreme snacking, experiencing stress with dieting, eating when bored, and skipping breakfast than noncarriers. | [72] |
| PER2, BMAL1, and NPAS2 | 189 patients with winter depression and 189 matched controls | PER2 rs10870, BMAL1 rs2290035 and NPAS2 rs11541353 significantly association with SAD | [73] |
| CRY1 rs10861688 | 260 cases with abdominal obesity and 260 controls, Chinese population | CRY1 rs10861688 T allele negatively associated with the risk of abdominal obesity. | [63] |
| REV-ERBα rs2314339 | 2212 subjects from two independent populations (1402 from Spanish Mediterranean and 810 North American) | Minor allele carriers (AA + AG) have lower probability of abdominal obesity than noncarriers. A allele carriers on low MUFA lead to high BMI while A carriers on high MUFA reduce BMI and BMI was low in A carriers in high-PUFA intake | [74] |
CLOCK (circadian locomotor output cycles kaput) BMAL1 (brain and muscle Arnt-Like protein-1) PER (Period), CRY (Cryptochrome), REV-ERBα (NR1D1 gene producing a protein called REV-ERBα), MUFA (mono-unsaturated fatty acid), SAD (Seasonal affective disorder), NPAS2 (Neuronal PAS Domain Protein 2).