Ethnic-Specific Genetic Association of Variants in the Corticotropin-Releasing Hormone Receptor 1 Gene with Nicotine Dependence

Abstract

Twin and family studies indicate that smoking addiction is highly influenced by genetic factors. Variants in the corticotropin-releasing hormone receptor 1 (CRHR1) gene have been associated with alcoholism and depression. In this study, we tested five single nucleotide polymorphisms (SNPs) in CRHR1 for their association with ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström test for ND (FTND) in 2,037 subjects from 602 families of either European American (EA) or African American (AA) ancestry. Association analysis of the five SNPs revealed a significant association of rs171440 with SQ in the AA sample and with SQ and FTND in the pooled AA and EA samples. Haplotype-based association analysis indicated significant association of haplotypes C-C (56.9%) and T-C (38.9%), formed by SNPs rs171440 and rs1396862, with SQ in the AA sample, C-C-G (47.6%) with SQ, and T-C-G (42.3%), formed by SNPs rs171440, rs1396862, and rs878886, with SQ and FTND in the pooled AA and EA samples. However, none of these associations remained significant after correction for multiple testing. Together, our results provide suggestive evidence for the involvement of CRHR1 in ND, which warrants further investigation using larger independent samples.

Examining sex differences in pleiotropic effects for depression and smoking using polygenic and gene‐region aggregation techniques

“…In contrast to previous research (e.g., Rogausch et al, 2007;Tang et al, 2015), genetic variation within the NR3C1 and CRHR1…”

“…For example, Rogausch, Kochen, Meineke, and Hennig (2007) found that G allele carriers at rs41423247 of NR3C1 were more likely to become smokers and had significantly higher daily cigarette consumption than C homozygotes. Other SNPs within NR3C2, FKBP5, and CRHR1 have also been examined in relation to smoking outcomes (dos Santos et al, 2012;Jensen et al, 2015;Koopmann et al, 2016;Rovaris et al, 2013;Tang et al, 2015), with mixed results. Interestingly, a small GWAS of daily cigarette use reported associations at SNPs within NR3C2, providing additional evidence that genes underlying HPA-axis function may also play a role in smoking behavior.…”

Targeting the Brain Stress Systems for the Treatment of Tobacco/Nicotine Dependence: Translating Preclinical and Clinical Findings

“…Although CRF activation is associated with mood regulation and depression in the clinic, very few studies in humans have examined the role of CRF mechanisms underlying tobacco dependence and stress-related smoking lapse behavior. A recent genetic study examined the CRHR1 gene, a gene encoding for the CRF 1 receptor, and whether variants in the CRHR1 gene were associated with nicotine dependence [37]. That study demonstrated a significant association between CRHR1 single nucleotide polymorphisms (SNPs) and smoking quantity in African American individuals, and a significant association between the same SNP and smoking quantity and Fagerstrom Test for Nicotine Dependence (FTND) scores in African American and European American individuals.…”