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. 2021 Jan-Dec:17:1744806921999924.
doi: 10.1177/1744806921999924.

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

Daisuke Nishizawa  1 , Masako Iseki  2 , Hideko Arita  3 , Kazuo Hanaoka  3 , Choku Yajima  3 , Jitsu Kato  4 , Setsuro Ogawa  5 , Ayako Hiranuma  1   6 , Shinya Kasai  1 , Junko Hasegawa  1 , Masakazu Hayashida  1   2 , Kazutaka Ikeda  1
Affiliations

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia

Daisuke Nishizawa et al. Mol Pain. 2021 Jan-Dec.

Abstract

Background: Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain.

Results: Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain (p ≥ 1.858 × 10-7), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p = 1.638 × 10-7). In the additional gene-based analysis, one gene, PRKCQ, was significantly associated with chronic pain in the trend model (adjusted p = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models.

Conclusions: These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.

Keywords: Genome-wide association study; chronic pain; gene-based/gene-set analysis; postherpetic neuralgia; single-nucleotide polymorphism.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kazutaka Ikeda has received support from Asahi Kasei Pharma Corporation for a project that is unrelated to this research and speaker’s and consultant’s fees from MSD K.K., VistaGen Therapeutics, Inc., Atheneum Partners Otsuka Pharmaceutical Co. Ltd., Taisho Pharmaceutical Co. Ltd., Eisai, Daiichi-Sankyo, Inc., Sumitomo Dainippon Pharma, Japan Tobacco, Inc., and Nippon Chemiphar. The authors declare no other conflicts of interest.

Figures

Figure 1.
Figure 1.
Manhattan plot of the GWAS results. (a) Plot of the analysis of all 191 patients with chronic pain in the trend model. (b) Plot of the analysis that including only patients with PHN. The red line indicates the threshold for a significant association.
Figure 2.
Figure 2.
Regional plot of a potent locus that was associated with PHN. The genomic region 400 kbp upstream and downstream of the rs4773840 SNP on chromosome 13 is illustrated. The results of the association analyses in each genetic model were plotted, with the information on annotated genes, estimated recombination rates, and the pairwise-calculated strength of linkage disequilibrium (LD; r2 values) with the rs4773840 SNP in this region.
Figure 3.
Figure 3.
Manhattan plot of the results of the gene-based analyses. (a) Plot of the analysis with all 191 patients with chronic pain in the trend model. (b) Plot of the analysis that included only patients with PHN. The dotted red line indicates the threshold for a significant association.
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