CRHR1 rs110405: Stress Response and Cortisol Regulation
The genetic variant rs110405 is a single nucleotide polymorphism located within an intron of the CRHR1 gene on chromosome 17. Research has linked this variant to individual differences in hypothalamic-pituitary-adrenal (HPA) axis dynamics, including the cortisol awakening response and stress-induced neuroendocrine reactivity. However, the scientific evidence supporting these associations remains limited and largely population-specific.
What each genotype means
Typical cortisol awakening response
You carry two copies of the C allele for rs110405 in the CRHR1 gene. In candidate gene investigations, this genotype has generally been linked with baseline neuroendocrine stress responses and typical cortisol reactivity patterns. However, overall evidence for single-locus effects remains limited, and variations in HPA-axis markers are heavily shaped by environmental factors and overall lifestyle.
Carried by roughly 55% to 60% of individuals of European ancestry, and represents the majority genotype in most global populations.
Intermediate stress hormone reactivity
You carry one copy of the T allele and one copy of the C allele for rs110405. Heterozygosity at this locus is part of a common CRHR1 haplotype block that has shown subtle associations with modified cortisol awakening response and stress reactivity in small cohorts. Findings across published studies are mixed, indicating that any individual physiological effect is modest at best.
Carried by approximately 35% to 40% of individuals of European ancestry, with lower frequencies observed in East Asian populations.
Altered stress hormone reactivity
You carry two copies of the minor T allele for rs110405 in the CRHR1 gene. Some research has linked this genotype or its broader haplotype to differences in cortisol awakening response and altered emotional reactivity following acute stress, especially in the presence of early-life stressors. Because scientific findings are associational and limited, this genotype alone does not determine or diagnose any stress-related condition.
Carried by roughly 6% to 8% of individuals of European ancestry, and is relatively uncommon or rare in several non-European ancestral groups.
Genomic Location and Variant Characteristics
The single nucleotide polymorphism rs110405 resides on human chromosome 17 within the corticotropin-releasing hormone receptor 1 (CRHR1) gene. This variant represents an intronic single-base change typically involving adenine (A) and guanine (G) alleles. Because it is located in a non-coding intronic region rather than an exon, rs110405 does not alter the primary amino acid sequence of the resulting receptor protein. Instead, genomic researchers evaluate such intronic polymorphisms for potential regulatory roles, such as altering transcriptional efficiency, pre-mRNA splicing patterns, or serving as genetic markers in tight linkage disequilibrium with other functional regulatory variants nearby.
The Biological Role of the CRHR1 Receptor
CRHR1 encodes a high-affinity G-protein coupled receptor that binds corticotropin-releasing hormone (CRH), which is released by the hypothalamus in response to physiological or psychological challenges. When CRH binds to its receptor in the anterior pituitary gland, it triggers the release of adrenocorticotropic hormone (ACTH), which subsequently signals the adrenal glands to synthesize and secrete cortisol into the bloodstream. This neuroendocrine cascade, known as the hypothalamic-pituitary-adrenal (HPA) axis, is the body's primary long-term hormonal stress response system. Variation in CRHR1 expression or receptor signaling can therefore subtly shift how sensitive the endocrine system is during acute stressors and across the diurnal circadian cycle.
Current Scientific Evidence and Limitations
Multiple candidate-gene investigations have evaluated CRHR1 polymorphisms, including rs110405 and its linked haplotype variants, for associations with stress responsiveness, the cortisol awakening response (CAR), and vulnerability to anxiety or mood disruptions following adversity. While some cohorts have demonstrated subtle differences in cortisol curve trajectories or affective reactivity, the overall evidentiary strength is classified as limited. Candidate gene associations in behavioral genomics frequently exhibit mixed replication across independent samples, varying based on study design, sex, and past exposure to environmental stressors. Large-scale genome-wide association studies (GWAS) have not established definitive, standalone causal links between rs110405 and clinical psychiatric conditions.
Population Distribution and Allele Frequencies
The alleles of rs110405 occur across global populations at varying rates. In datasets such as the Genome Aggregation Database (gnomAD), the minor allele frequency is approximately 0.25 among individuals of European ancestry. Frequencies differ across other ancestral groups, reflecting standard patterns of human genetic divergence. Because the variant often forms broader ancestral haplotype blocks alongside other common CRHR1 markers (such as rs110402 and rs242924), its prevalence and co-occurrence patterns must be interpreted within the specific ancestral background of the individual tested.
Interpreting Your Results Responsibly
A person's genotype at rs110405 is not a diagnostic test, nor does it predict how an individual will feel or cope when confronting difficult circumstances. Stress physiology and psychological health are profoundly polygenic traits shaped by thousands of subtle genetic inputs interacting with childhood environment, social support, lifestyle, sleep hygiene, and active coping mechanisms. Possessing any particular genotype does not guarantee heightened stress sensitivity, nor does it confer absolute resilience. This genetic information is educational and should never be used to initiate, alter, or discontinue any medical or psychological treatment.
How common is this variant?
The minor allele frequency for rs110405 is approximately 0.25 in individuals of European ancestry according to gnomAD data, with varying distribution across other ancestral backgrounds.
Frequently asked questions
What is CRHR1 rs110405?
The rs110405 variant is an intronic single nucleotide polymorphism in the CRHR1 gene, which encodes a key receptor in the body's neuroendocrine stress response system.
Does having the minor allele mean I have high stress?
No. The variant has only been weakly associated with subtle statistical differences in cortisol patterns in specific research settings. It cannot diagnose or predict how stressed, anxious, or calm an individual feels.
Can this genetic variant determine psychiatric disorders?
No, rs110405 does not cause or determine conditions such as depression or anxiety. Complex psychiatric traits result from intricate interactions between thousands of genetic variants and environmental factors like life events, trauma, and lifestyle.
Should I change any medications based on rs110405?
No. There are no clinical pharmacogenetic guidelines (such as CPIC recommendations) that guide medication dosing or selection based on rs110405. Any questions regarding medications or stress management should be discussed directly with a qualified healthcare provider.
Sources & further reading
Educational information only, last refreshed 9/12/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Variant in the corticotropin-releasing hormone receptor 1 gene that moderates hypothalamic-pituitary-adrenal axis reactivity and vulnerability to stress-induced mood disturbances.
Intronic CRHR1 variant associated with neuroendocrine stress sensitivity.
Tag variant in the CRHR1 locus associated with HPA axis regulation.