rs806377

This international doctoral thesis examined gene-physical activity interactions in fibromyalgia through six studies analyzing 64 SNPs across 34 candidate genes in Spanish women. The case-control study (314 fibromyalgia cases vs. 112 controls) identified associations of rs841 (GCH1), rs1799971 (OPRM1), and rs2097903 (COMT) with fibromyalgia susceptibility (p=0.04, p=0.02, and p=0.04 respectively). Cross-sectional studies (n=274-276 fibromyalgia patients) found that SCN9A rs4453709 and other genetic polymorphisms interacted with physical activity to influence pain, fatigue, and resilience outcomes.

This case-control association study analyzed five CNR1 gene polymorphisms (rs806368, rs1049353, rs806371, rs806377, rs1535255) in 319 major depression patients and 150 healthy controls, plus a pharmacogenetic subsample of 155 depressed patients treated with citalopram. The rs806371 G carrier genotype showed higher frequency in MD with melancholia (p=0.018) and psychotic symptoms (p=0.007). For treatment response, rs806368 and rs806371 TT homozygotes had increased risk of no remission at 12 weeks (OR=2.64 and OR=2.8, respectively). A significant time-sex-genotype interaction was found for rs806368, with C carrier men showing better antidepressant response throughout follow-up (p=0.026).

This association study examined polymorphisms in the cannabinoid receptor 1 (CNR1) gene and cannabis dependence in 1,923 individuals from the COGA family study. Two SNPs showed significant association with DSM-III-R cannabis dependence: rs806380 (p=0.009) and rs806368 (p=0.05), with rs806380 driving the haplotype association. Results support a role for CNR1 variation in cannabis dependence risk.

Association study of the cannabinoid receptor gene (CNR1) in two independent samples found a haplotype (C-G2) significantly associated with ADHD in Finnish adolescents (P = 0.008), with a threefold increased risk in males. A single SNP (rs1049353, allele A, P = 0.011) and alternative haplotype (C-A1, P = 0.04) were associated with post-traumatic stress disorder in LA Caucasian parents, suggesting CNR1 may be a risk factor for ADHD and possibly PTSD.

This association study examined four SNPs in the CNR1 gene (encoding the cannabinoid receptor) in 541 adolescents (327 cases with cannabis dependence symptoms, 214 controls without symptoms). SNP rs806380 (A/G, located in intron 2) showed significant association with protection from cannabis dependence symptoms (p=0.034, protective effect for G allele). A common haplotype (GGCC, present in 21% of subjects) was significantly associated with fewer cannabis dependence symptoms in the overall sample (LRT=16.47, p=0.021), though effects were attenuated in stratified ethnic analyses.

This doctoral thesis conducted multiple candidate gene association studies in 274-426 southern Spanish women with fibromyalgia to investigate gene-physical activity/sedentary behavior interactions with pain, fatigue, and resilience. Study III identified rs841 (GCH1) GG genotype (OR=0.61, p=0.04) and rs2097903 (COMT) AT/TT genotypes (OR=1.66, p=0.04) associated with fibromyalgia susceptibility, and confirmed rs1799971 (OPRM1) GG genotype (OR=0.58, p=0.02) confers genetic risk. Study IV found rs6311/rs6313 (HTR2A) polymorphisms individually associated with algometer pain score, and gene-sedentary behavior interactions involving rs4680/rs165599 (COMT), rs1383914 (ADRA1A), rs12994338/rs4453709 (SCN9A), and rs6860 (CHMP1A) significantly associated with pain outcomes. SCN9A emerged as most robust gene for fibromyalgia phenotype.