Research

Hormones & Sleep

How your genes affect thyroid conversion, sex hormones, sleep timing, and caffeine sensitivity

This category covers thyroid hormone activation (DIO1, DIO2), sex hormone binding and metabolism (SHBG, CYP19A1, SRD5A2, CYP17A1), estrogen receptor sensitivity (ESR1), clock genes and chronotype (CLOCK, PER3, PER2), melatonin signaling (MTNR1B, ASMT), caffeine metabolism (ADORA2A, AHR), and arousal regulation (NPSR1). These variants influence thyroid medication response, hormone balance, sleep timing, and stimulant sensitivity.

Genetic Variants (17)

rs225014

(DIO2 Thr92Ala)

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

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rs11206244

(DIO1 C785T)

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

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rs1799941

(SHBG)

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

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rs700518

(CYP19A1 Val80)

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

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rs523349

(SRD5A2 V89L)

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

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rs743572

(CYP17A1 -34 T>C)

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

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rs2234693

(ESR1 PvuII)

Estrogen receptor alpha intron variant affecting receptor expression and estrogen sensitivity

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rs1801260

(CLOCK 3111T>C (3'UTR))

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

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rs228697

(PER3 Pro864Ala)

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

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rs2304672

(PER2 5'UTR C111G)

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

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rs10830963

(MTNR1B Intron C>G)

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

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rs4446909

(ASMT Promoter A>G)

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

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rs5751876

(ADORA2A 1976T>C)

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

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rs2066853

(AHR Arg554Lys)

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

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rs324981

(NPSR1 Asn107Ile)

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

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rs1991517

(TSHR Asp727Glu)

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

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rs2287161

(CRY1 3' Downstream G>C)

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

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