rs1801260

This association study examined nine functional SNPs in circadian positive feedback loop genes (CLOCK, BMAL1, NPAS2) in 704 Chinese gastric cancer patients. Three SNPs showed significant associations with overall survival and recurrence-free survival: rs11133399 in CLOCK (HR 1.27-1.29, p=0.007-0.020), rs2279284 in BMAL1 (HR 1.12-1.18, p=0.024-0.048), and rs1044432 in BMAL1 (HR 0.82-0.84, p=0.042-0.047). Functional assays confirmed that the G allele of rs11133399 enhanced CLOCK promoter activity and gene expression.

This cross-sectional candidate gene study examined 14 tag SNPs in 7 circadian genes for association with osteoporosis risk in 597 Chinese geriatric subjects. CRY2 rs2292910 showed protective effects (AC genotype OR=0.647, p=0.044), while MTNR1B rs3781638 showed increased risk (GG genotype OR=2.058, p=0.044). The findings suggest circadian gene variants may influence bone mineral density and osteoporosis susceptibility.

This scoping review examined 18 observational studies (n=26,684) from low- and middle-income countries investigating gene-environment interactions affecting obesity risk. The review found statistically significant associations for 12 individual SNPs including FTO rs1421085, rs9939609, rs10163409, rs3751812, MC4R rs17782313, rs12970134, TMEM18 rs7561317, NEGR1 rs2815752, CARTPT rs2239670, UCP2 rs659366, CLOCK rs1801260, and FLJ33544 rs140133294, though most associations were not replicated across different populations and environmental exposures.

This dissertation examined pharmacogenetic associations with clozapine adverse effects in 237 Finnish schizophrenia patients. ADRA2A rs1800544 was associated with clozapine-induced sialorrhea (OR 2.13, 95% CI: 1.17-3.88, p=0.013). Eight HNMT SNPs in complete linkage disequilibrium (r²=1) were associated with sedation. CHRM3 rs685548 and weighted genetic risk scores from HTR4, HTR7, TPH1, CHRM2, ABCB1, and OPRM1 were associated with anticholinergic symptoms.

Handbook of Experimental Pharmacology (Volume 217) providing comprehensive review of circadian clock biology and its role in health and disease. Discusses molecular mechanisms of circadian regulation, circadian control of metabolism, sleep, hormones, and behavior, and applications to pharmacotherapy including cancer chronotherapy. Reviews genetic variants in circadian genes (CLOCK rs1801260 and rs4580704, MTNR1A rs2119882, MTNR1B rs3781637) associated with metabolic traits and disease susceptibility, and circadian clock gene mutations linked to cancer risk and metabolic disorders.

This prospective cohort study of 609 breast cancer cases and 1,216 matched controls from the Nurses' Health Study II found no main effect of 178 common variants in circadian and melatonin metabolism genes on breast cancer risk. However, it identified a significant gene-environment interaction between NPAS2 Ala394Thr (rs2305160) and rotating shift-work exposure: among women with ≥2 years of night shift work, the Thr/Thr genotype was associated with a 2.83-fold increased breast cancer risk (OR=2.83, 95% CI: 1.47-5.56) compared to the Thr/Thr genotype with minimal shift exposure.

This family-based association study examined 15 circadian genes in 1,158 individuals (70 trios and 237 quads in Sample II) to investigate genetic susceptibility to bipolar disorder. Three CLOCK gene SNPs showed nominally significant association with BP (rs534654 p=0.0097, rs6850524 p=0.012, rs4340844 p=0.015). Most importantly, a significant multi-locus interaction between rs6442925 in BHLHB2, rs1534891 in CSNK1E, and rs534654 near the CLOCK gene was identified (p=0.00000172), which remained significant after correction for multiple testing using the False Discovery Rate method (FDR p=0.00000177).

This review of molecular genetic studies of ADHD in Han Chinese populations summarizes candidate gene studies across dopaminergic, noradrenergic, serotonergic, and enzymatic systems, along with the first GWAS in Chinese ADHD cases (n=1040) and controls (n=963). While no single gene has been definitively identified, significant associations include DRD4 7-repeat allele (OR=1.70, 95% CI 1.20-2.40, p=0.003 in males), DBH rs2519152, and various polymorphisms in COMT, NET1, and serotonin genes, though results remain inconsistent across studies.

In a cross-sectional study of 2,157 European subjects, rs10462028 in the CLOCK circadian gene showed a significant gene-by-environment interaction with financial hardship on migraine susceptibility (p=0.006 in recessive model), with a crossover pattern where the AA genotype was protective under severe financial stress but a risk factor under financial comfort. The effect remained after controlling for depression and was replicated in the Budapest subsample. In silico analysis revealed rs10462028 affects microRNA binding sites that regulate CLOCK expression.

This review examines molecular genetic studies of attention-deficit hyperactivity disorder (ADHD) in Han Chinese samples, including candidate gene studies, endophenotype research, genome-wide association studies, and pharmacogenomic investigations. Eight GWAS conducted for ADHD have been inconclusive with no genome-wide significant associations identified, though candidate gene studies have identified associations with dopaminergic (DAT1, DRD4, DRD2, DRD3), noradrenergic (NET1, ADRA2A, ADRA2C), serotonergic (SLC6A4, HTR genes), and metabolic pathway genes (COMT, MAOA, MAOB, DBH, TPH). A meta-analysis of DRD4 longer repeats showed OR=1.70-1.74 in males with ADHD-C subtype.