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| Chinese Medical Journal, 2012, Vol. 125 No. 6:1127-1134 |
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| 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,
Shawn Levy ,
Henry R. Kranzler,
Lindsay A. Farrer,,
Joel Gelernter,
Robert R.Recker,
DENG Hong-wen,
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Free Full Text [  HTML
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| Keywords:
No. R21 AA015973, No. R21 AG027110, No. R01 AR050496-01, No. R01 AG026564, and No. P50 AR055081·No. 30771222 and No. 30731160618·(2010) 609·No. 2011TF1004 |
| Abstract: |
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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.
Chinese Medical Journal 2012;125(6):1127-1134
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This study was supported by : NIH National Science Foundation of China() Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China() Innovative Program of Hunan Province() |
| Free Full Text [ HTML
| PDF(567K)
] Abstract download [TXT | XML] |
CHEN Xiang-ding Laboratory of Molecular and Statistical Genetics, Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Institute of Biology, Hunan Normal University, Changsha, Hunan 410081, China;
XIONG Dong-hai
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, MO 64108, USA;
YANG Tie-lin
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, MO 64108, USA;
PEI Yu-fang
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, MO 64108, USA;
GUO Yan-fang
Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shannxi 710049, China;
LI Jian
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, MO 64108, USA;
YANG Fang
Laboratory of Molecular and Statistical Genetics, Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Institute of Biology, Hunan Normal University, Changsha, Hunan 410081, China;
PAN Feng,
Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shannxi 710049, China;
TAN Li-jun
Laboratory of Molecular and Statistical Genetics, Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Institute of Biology, Hunan Normal University, Changsha, Hunan 410081, China;
YAN Han
Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shannxi 710049, China;
LIU Xiao-gang
Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shannxi 710049, China;
LEI Shu-feng
Laboratory of Molecular and Statistical Genetics, Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Institute of Biology, Hunan Normal University, Changsha, Hunan 410081, China;
LI Xi
Laboratory of Molecular and Statistical Genetics, Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Institute of Biology, Hunan Normal University, Changsha, Hunan 410081, China;
NING Ling-ling
Laboratory of Molecular and Statistical Genetics, Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Institute of Biology, Hunan Normal University, Changsha, Hunan 410081, China;
ZHU Xue-zhen
Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shannxi 710049, China;
Shawn Levy
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA;
Henry R. Kranzler
University of Connecticut Health Center, Farmington, CT 06030, USA;
Lindsay A. Farrer,
Boston University School of Medicine, Boston, MA 02118, USA;
Joel Gelernter
Department of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA;
Robert R.Recker
Osteoporosis research Center, Creighton University, Omaha, NE 68131, USA;
DENG Hong-wen
Laboratory of Molecular and Statistical Genetics, Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Institute of Biology, Hunan Normal University, Changsha, Hunan 410081, China;
Correspondence to:
DENG Hong-wen
College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China
(Tel:86-731-88872791 Email:hwdeng@hunnu.edu.cn )
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