Genome-Wide Association Study of Serum Prostate-Specific Antigen Levels Based on 1000 Genomes Imputed Data in Japanese: The Japan Multi-Institutional Collaborative Cohort Study

Asahi Hishida, Masahiro Nakatochi, Takashi Tamura, Mako Nagayoshi, Rieko Okada, Yoko Kubo, Mineko Tsukamoto, Yuka Kadomatsu, Sadao Suzuki, Takeshi Nishiyama, Nagato Kuriyama, Isao Watanabe, Toshiro Takezaki, Daisaku Nishimoto, Kiyonori Kurik, Kokichi Arisawa, Sakurako Katsuura Kamano, Haruo Mikami, Miho Kusakabe, Isao OzeYuriko N. Koyanagi, Yasuyuki Nakamura, Aya Kadota, Chisato Shimanoe, Keitaro Tanaka, Hiroaki Ikezaki, Masayuki Murata, Michiaki Kubo, Yukihide Momozawa, Kenji Takeuchi, Kenji Wakai

Research output: Contribution to journalArticlepeer-review

Abstract

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study,we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P <5×10∑8), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance (P <1×10∑6). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SGMS2 SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of KLK3 SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.

Original languageEnglish
Pages (from-to)183-194
Number of pages12
JournalNagoya journal of medical science
Volume83
Issue number1
DOIs
Publication statusPublished - 2021

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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