Hormones & Sleep

Affects conversion of inactive T4 to active T3 thyroid hormone in brain, pituitary, and peripheral tissues

Common variant in the 3' UTR of the DIO1 gene affecting thyroid hormone metabolism and T3/T4 ratio

Promoter region variant affecting sex hormone-binding globulin levels, with the A allele increasing SHBG by 15-25% and influencing free testosterone and estradiol bioavailability

Synonymous variant in aromatase gene affecting estrogen production, bone density, and response to aromatase inhibitors

Missense variant reducing 5-alpha-reductase type 2 enzyme activity, affecting DHT production and response to finasteride

Promoter variant affecting 17α-hydroxylase expression and steroid hormone synthesis, influencing cortisol, DHEA, androgen, and estrogen production

Estrogen receptor alpha intron variant affecting receptor expression and estrogen sensitivity

Core circadian clock transcription factor variant affecting mRNA stability, associated with evening preference, delayed sleep onset, and shorter sleep duration

Core clock gene variant that shifts circadian period length and influences morning vs evening chronotype

Regulatory variant in a core clock gene that influences circadian timing, sleep-wake preference, and reward processing

Melatonin receptor variant that extends nighttime melatonin signaling in pancreatic beta cells, impairing glucose-stimulated insulin secretion — especially when meals are eaten late

Final enzyme in melatonin synthesis; promoter variant reduces ASMT expression and lowers melatonin production, affecting sleep onset and circadian rhythm

Adenosine A2A receptor variant that determines individual sensitivity to caffeine's effects on anxiety and sleep

Aryl hydrocarbon receptor variant in the transactivation domain that alters AHR signaling, affecting CYP1A2 inducibility, caffeine metabolism patterns, and circadian clock interactions

Gain-of-function missense variant in the neuropeptide S receptor that increases receptor signaling ~10-fold, promoting wakefulness and reducing sleep duration

Affects TSH receptor sensitivity and thyroid hormone regulation; influences TSH levels, metabolic function, and congenital hypothyroidism risk

Cryptochrome 1 circadian gene variant influencing glucose metabolism, sleep timing, mood regulation, and metabolic responses to diet

Synonymous exon-10 variant that triggers alternative splicing of the G-protein beta-3 subunit, amplifying signaling through virtually every GPCR — affecting blood pressure, weight regulation, hormonal responses, sleep timing, and antidepressant efficacy

Modulates local cortisol activation from cortisone in liver and adipose tissue, influencing visceral fat, insulin sensitivity, and metabolic syndrome risk

Affects FSH receptor sensitivity, determining ovarian response to FSH stimulation and influencing fertility treatment dosing in both women and men

Strongest GWAS thyroid locus — regulatory variant near FOXE1 affecting thyroid development, TSH levels, and differentiated thyroid cancer risk

Missense variant in core circadian clock gene PER2 that lengthens intrinsic circadian period and shifts chronotype toward eveningness

Circadian clock gene variant affecting fasting glucose, hepatic lipid metabolism, and seasonal metabolic responses

Missense variant in circadian clock gene PER3 associated with morning chronotype preference and earlier diurnal timing