ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior

Xiang Ding Chen, Dong Hai Xiong, Tie Lin Yang, Yu Fang Pei, Yan Fang Guo, Jian Li, Fang Yang, Feng Pan, Li Jun Tan, Han Yan, Xiao Gang Liu, Shu Feng Lei, Xi Li, Ling Ling Ning, Xue Zhen Zhu, Shawn Levy, Henry R. Kranzler, Lindsay A. Farrer, Joel Gelernter, Robert R. Recker & 1 others Hong Wen Deng

Research output: Contribution to journalArticle

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Abstract

Background: Alcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology. Methods: A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans. Results: Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51×10- 8). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption. Conclusion: The evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.

Original languageEnglish
Pages (from-to)1127-1134
Number of pages8
JournalChinese Medical Journal
Volume125
Issue number6
DOIs
StatePublished - 2012

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Ankyrin Repeat
Drinking Behavior
Alcohol Drinking
Cytokines
Genes
Genome-Wide Association Study
Alcoholism
Nuclear Family
Single Nucleotide Polymorphism
Alcohols
Phenotype
Disease Susceptibility
Haplotypes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Chen, X. D., Xiong, D. H., Yang, T. L., Pei, Y. F., Guo, Y. F., Li, J., ... Deng, H. W. (2012). ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior. Chinese Medical Journal, 125(6), 1127-1134. https://doi.org/10.3760/cma.j.issn.0366-6999.2012.06.029

ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior. / Chen, Xiang Ding; Xiong, Dong Hai; Yang, Tie Lin; Pei, Yu Fang; Guo, Yan Fang; Li, Jian; Yang, Fang; Pan, Feng; Tan, Li Jun; Yan, Han; Liu, Xiao Gang; Lei, Shu Feng; Li, Xi; Ning, Ling Ling; Zhu, Xue Zhen; Levy, Shawn; Kranzler, Henry R.; Farrer, Lindsay A.; Gelernter, Joel; Recker, Robert R.; Deng, Hong Wen.

In: Chinese Medical Journal, Vol. 125, No. 6, 2012, p. 1127-1134.

Research output: Contribution to journalArticle

Chen, XD, Xiong, DH, Yang, TL, Pei, YF, Guo, YF, Li, J, Yang, F, Pan, F, Tan, LJ, Yan, H, Liu, XG, Lei, SF, Li, X, Ning, LL, Zhu, XZ, Levy, S, Kranzler, HR, Farrer, LA, Gelernter, J, Recker, RR & Deng, HW 2012, 'ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior', Chinese Medical Journal, vol. 125, no. 6, pp. 1127-1134. https://doi.org/10.3760/cma.j.issn.0366-6999.2012.06.029
Chen, Xiang Ding ; Xiong, Dong Hai ; Yang, Tie Lin ; Pei, Yu Fang ; Guo, Yan Fang ; Li, Jian ; Yang, Fang ; Pan, Feng ; Tan, Li Jun ; Yan, Han ; Liu, Xiao Gang ; Lei, Shu Feng ; Li, Xi ; Ning, Ling Ling ; Zhu, Xue Zhen ; Levy, Shawn ; Kranzler, Henry R. ; Farrer, Lindsay A. ; Gelernter, Joel ; Recker, Robert R. ; Deng, Hong Wen. / ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior. In: Chinese Medical Journal. 2012 ; Vol. 125, No. 6. pp. 1127-1134.
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abstract = "Background: Alcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology. Methods: A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans. Results: Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51×10- 8). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption. Conclusion: The evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.",
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T1 - ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior

AU - Chen, Xiang Ding

AU - Xiong, Dong Hai

AU - Yang, Tie Lin

AU - Pei, Yu Fang

AU - Guo, Yan Fang

AU - Li, Jian

AU - Yang, Fang

AU - Pan, Feng

AU - Tan, Li Jun

AU - Yan, Han

AU - Liu, Xiao Gang

AU - Lei, Shu Feng

AU - Li, Xi

AU - Ning, Ling Ling

AU - Zhu, Xue Zhen

AU - Levy, Shawn

AU - Kranzler, Henry R.

AU - Farrer, Lindsay A.

AU - Gelernter, Joel

AU - Recker, Robert R.

AU - Deng, Hong Wen

PY - 2012

Y1 - 2012

N2 - Background: Alcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology. Methods: A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans. Results: Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51×10- 8). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption. Conclusion: The evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.

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