rs110402

A candidate gene association study of 368 healthy adults examined genetic variation in FKBP5 and CRHR1 in relation to cortisol response to acute psychosocial stress (Trier Social Stress Test). rs4713902 in FKBP5 showed the strongest association with baseline cortisol (p=0.0004, dominant model). Three CRHR1 SNPs (rs7209436, rs110402, rs242924) were associated with peak cortisol response (p=0.0029-0.0047, recessive models). Sex-specific effects and interactions with trait anxiety were observed.

This Japanese case-control study examined 12 SNPs in CRHR1 and CRHR2 genes in 173 major depressive disorder (MDD) patients, 180 panic disorder (PD) patients, and 285 healthy controls. SNP rs110402 in CRHR1 showed association with MDD (p=0.001, OR=1.81), as did rs242924 in CRHR1 for both MDD (p=0.013) and PD (p=0.022, OR=1.55). SNP rs3779250 in CRHR2 showed strong association with MDD (p=1.75e-11, OR=2.83). Haplotype analyses identified T-A-T-G-G and T-A haplotypes in CRHR1 associated with MDD, and C-C haplotype in CRHR2 associated with PD.

This gene-environment interaction study examined 460 women including FMR1 premutation carriers to test whether CRHR1 polymorphisms moderate the relationship between raising a child with Fragile X Syndrome and anxiety/depression symptoms. A significant interaction was identified between rs7209436 genotype and FXS child status in predicting social anxiety scores (P = 0.0001), suggesting that CRHR1 genetic variants influencing cortisol activation modulate anxiety responses to the stress of raising a child with FXS.

Gene-by-gene-by-environment study of 1,392 African-American participants examining interactions between CRHR1 (rs110402, TCA haplotype) and 5-HTTLPR polymorphisms with childhood abuse on depressive symptoms. Found significant interactions: CRHR1 rs110402 with abuse predicting depression (N=1,059, P=0.0089), and combined 5-HTTLPR and CRHR1 interaction with abuse on depressive symptoms (N=856, P=0.016), suggesting genetic risk alleles in both genes increase depression severity at lower abuse levels.

This study examined gene-environment (G×E) interactions between HPA axis variants (CRHR1, NR3C1, FKBP5) and childhood trauma on anxiety sensitivity in South African adolescents (n=951). Significant associations and interactions were found in gender- and ethnicity-specific analyses, including FKBP5 rs9296158 (p=0.025) and rs737054 (p=0.045) in Coloured males, and protective effects of NR3C1 rs190488 (p=0.009) and rs10482605 (p=0.036) with increasing trauma in Xhosa participants.

This review examines gene-environment interactions in stress-related psychiatric disorders, focusing on CRHR1 and FKBP5 genes. Authors report that CRHR1 polymorphisms (rs7209436, rs110402, rs242924) interact with childhood abuse to predict adult depression, while FKBP5 variants (rs3800373, rs9296158) interact with child abuse to predict adult PTSD symptoms. The paper integrates human genetic association findings with preclinical research on amygdala-HPA axis development, proposing a model where gene-environment interactions during developmental critical periods mediate stress resilience and psychiatric vulnerability.

This replication study tested a gene × environment interaction between childhood maltreatment and CRHR1 gene variants (TAT haplotype formed by rs7209436, rs110402, rs242924) predicting adult depression. In the E-Risk Study of 1,116 women, the TAT haplotype showed significant protective effects (OR=1.73-9.27 for past-year MDD, OR=1.92-8.61 for recurrent MDD depending on haplotype copies). However, the Dunedin Study of 1,037 individuals did not replicate this gene × environment finding, suggesting the effect may depend on how maltreatment is measured (emotional memories vs. factual reports).

This gene-environment interaction study examined 422 African American adults (and validated findings in 199 Caucasian women) to assess how CRHR1 gene polymorphisms moderate the effect of child abuse on adult depression. The study found significant gene-environment interactions with multiple SNPs including rs110402 (P=.008) and a protective haplotype in intron 1 (P<.001), where individuals carrying protective alleles of rs110402 and rs7209436 showed markedly lower depression scores (BDI=10.22) despite moderate-to-severe childhood abuse, compared to those with common alleles (BDI=22.33-22.49).

This cross-sectional study of 762 African American adults found that four FKBP5 SNPs (rs9296158, rs3800373, rs1360780, rs9470080; minimum P=0.0004) significantly interacted with severity of childhood abuse to predict adult PTSD symptoms, independent of non-child abuse trauma exposure, depression severity, age, sex, and genetic ancestry. The SNPs showed no main effects on PTSD or interactions with non-child abuse trauma, suggesting a specific gene-by-childhood-environment interaction mechanism.