Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Daisuke Nishizawa, Shinya Kasai, Junko Hasegawa, Naomi Sato, Hidetaka Yamada, Fumihiko Tanioka, Makoto Nagashima, Ryoji Katoh, Yasuo Satoh, Megumi Tagami, Hiroshi Ujike, Norio Ozaki, Toshiya Inada, Nakao Iwata, Ichiro Sora, Masaomi Iyo, Mitsuhiko Yamada, Naoki Kondo, Moo Jun Won, Nobuya NaruseKumi Uehara-Aoyama, Masanari Itokawa, Kazutaka Ohi, Ryota Hashimoto, Kumpei Tanisawa, Tomio Arai, Seijiro Mori, Motoji Sawabe, Makiko Naka-Mieno, Yoshiji Yamada, Miki Yamada, Noriko Sato, Masaaki Muramatsu, Masashi Tanaka, Yoko Irukayama-Tomobe, Yuki C. Saito, Takeshi Sakurai, Masakazu Hayashida, Haruhiko Sugimura, Kazutaka Ikeda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. Results: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. Conclusions: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.

Original languageEnglish
Article number50
JournalMolecular brain
Volume8
Issue number1
DOIs
Publication statusPublished - 20-08-2015

Fingerprint

Orexin Receptors
Tobacco Use Disorder
Genome-Wide Association Study
Genes
Single Nucleotide Polymorphism
Personality
Methamphetamine
Goiter
Tobacco Products
Genome
Postoperative Pain
Psychotic Disorders
Population
Autopsy

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Nishizawa, Daisuke ; Kasai, Shinya ; Hasegawa, Junko ; Sato, Naomi ; Yamada, Hidetaka ; Tanioka, Fumihiko ; Nagashima, Makoto ; Katoh, Ryoji ; Satoh, Yasuo ; Tagami, Megumi ; Ujike, Hiroshi ; Ozaki, Norio ; Inada, Toshiya ; Iwata, Nakao ; Sora, Ichiro ; Iyo, Masaomi ; Yamada, Mitsuhiko ; Kondo, Naoki ; Won, Moo Jun ; Naruse, Nobuya ; Uehara-Aoyama, Kumi ; Itokawa, Masanari ; Ohi, Kazutaka ; Hashimoto, Ryota ; Tanisawa, Kumpei ; Arai, Tomio ; Mori, Seijiro ; Sawabe, Motoji ; Naka-Mieno, Makiko ; Yamada, Yoshiji ; Yamada, Miki ; Sato, Noriko ; Muramatsu, Masaaki ; Tanaka, Masashi ; Irukayama-Tomobe, Yoko ; Saito, Yuki C. ; Sakurai, Takeshi ; Hayashida, Masakazu ; Sugimura, Haruhiko ; Ikeda, Kazutaka. / Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies. In: Molecular brain. 2015 ; Vol. 8, No. 1.
@article{b3d011e5f573480991c52bbbed6488a2,
title = "Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies",
abstract = "Background: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. Results: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerstr{\"o}m Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. Conclusions: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.",
author = "Daisuke Nishizawa and Shinya Kasai and Junko Hasegawa and Naomi Sato and Hidetaka Yamada and Fumihiko Tanioka and Makoto Nagashima and Ryoji Katoh and Yasuo Satoh and Megumi Tagami and Hiroshi Ujike and Norio Ozaki and Toshiya Inada and Nakao Iwata and Ichiro Sora and Masaomi Iyo and Mitsuhiko Yamada and Naoki Kondo and Won, {Moo Jun} and Nobuya Naruse and Kumi Uehara-Aoyama and Masanari Itokawa and Kazutaka Ohi and Ryota Hashimoto and Kumpei Tanisawa and Tomio Arai and Seijiro Mori and Motoji Sawabe and Makiko Naka-Mieno and Yoshiji Yamada and Miki Yamada and Noriko Sato and Masaaki Muramatsu and Masashi Tanaka and Yoko Irukayama-Tomobe and Saito, {Yuki C.} and Takeshi Sakurai and Masakazu Hayashida and Haruhiko Sugimura and Kazutaka Ikeda",
year = "2015",
month = "8",
day = "20",
doi = "10.1186/s13041-015-0142-x",
language = "English",
volume = "8",
journal = "Molecular Brain",
issn = "1756-6606",
publisher = "BioMed Central",
number = "1",

}

Nishizawa, D, Kasai, S, Hasegawa, J, Sato, N, Yamada, H, Tanioka, F, Nagashima, M, Katoh, R, Satoh, Y, Tagami, M, Ujike, H, Ozaki, N, Inada, T, Iwata, N, Sora, I, Iyo, M, Yamada, M, Kondo, N, Won, MJ, Naruse, N, Uehara-Aoyama, K, Itokawa, M, Ohi, K, Hashimoto, R, Tanisawa, K, Arai, T, Mori, S, Sawabe, M, Naka-Mieno, M, Yamada, Y, Yamada, M, Sato, N, Muramatsu, M, Tanaka, M, Irukayama-Tomobe, Y, Saito, YC, Sakurai, T, Hayashida, M, Sugimura, H & Ikeda, K 2015, 'Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies', Molecular brain, vol. 8, no. 1, 50. https://doi.org/10.1186/s13041-015-0142-x

Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies. / Nishizawa, Daisuke; Kasai, Shinya; Hasegawa, Junko; Sato, Naomi; Yamada, Hidetaka; Tanioka, Fumihiko; Nagashima, Makoto; Katoh, Ryoji; Satoh, Yasuo; Tagami, Megumi; Ujike, Hiroshi; Ozaki, Norio; Inada, Toshiya; Iwata, Nakao; Sora, Ichiro; Iyo, Masaomi; Yamada, Mitsuhiko; Kondo, Naoki; Won, Moo Jun; Naruse, Nobuya; Uehara-Aoyama, Kumi; Itokawa, Masanari; Ohi, Kazutaka; Hashimoto, Ryota; Tanisawa, Kumpei; Arai, Tomio; Mori, Seijiro; Sawabe, Motoji; Naka-Mieno, Makiko; Yamada, Yoshiji; Yamada, Miki; Sato, Noriko; Muramatsu, Masaaki; Tanaka, Masashi; Irukayama-Tomobe, Yoko; Saito, Yuki C.; Sakurai, Takeshi; Hayashida, Masakazu; Sugimura, Haruhiko; Ikeda, Kazutaka.

In: Molecular brain, Vol. 8, No. 1, 50, 20.08.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

AU - Nishizawa, Daisuke

AU - Kasai, Shinya

AU - Hasegawa, Junko

AU - Sato, Naomi

AU - Yamada, Hidetaka

AU - Tanioka, Fumihiko

AU - Nagashima, Makoto

AU - Katoh, Ryoji

AU - Satoh, Yasuo

AU - Tagami, Megumi

AU - Ujike, Hiroshi

AU - Ozaki, Norio

AU - Inada, Toshiya

AU - Iwata, Nakao

AU - Sora, Ichiro

AU - Iyo, Masaomi

AU - Yamada, Mitsuhiko

AU - Kondo, Naoki

AU - Won, Moo Jun

AU - Naruse, Nobuya

AU - Uehara-Aoyama, Kumi

AU - Itokawa, Masanari

AU - Ohi, Kazutaka

AU - Hashimoto, Ryota

AU - Tanisawa, Kumpei

AU - Arai, Tomio

AU - Mori, Seijiro

AU - Sawabe, Motoji

AU - Naka-Mieno, Makiko

AU - Yamada, Yoshiji

AU - Yamada, Miki

AU - Sato, Noriko

AU - Muramatsu, Masaaki

AU - Tanaka, Masashi

AU - Irukayama-Tomobe, Yoko

AU - Saito, Yuki C.

AU - Sakurai, Takeshi

AU - Hayashida, Masakazu

AU - Sugimura, Haruhiko

AU - Ikeda, Kazutaka

PY - 2015/8/20

Y1 - 2015/8/20

N2 - Background: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. Results: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. Conclusions: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.

AB - Background: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. Results: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. Conclusions: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.

UR - http://www.scopus.com/inward/record.url?scp=84939513307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939513307&partnerID=8YFLogxK

U2 - 10.1186/s13041-015-0142-x

DO - 10.1186/s13041-015-0142-x

M3 - Article

C2 - 26289589

AN - SCOPUS:84939513307

VL - 8

JO - Molecular Brain

JF - Molecular Brain

SN - 1756-6606

IS - 1

M1 - 50

ER -