title: Genetic variants in the CPNE5 gene are associated with alcohol dependence and obesity in Caucasian populations.
abstract: Alcohol addiction may increase the risk of obesity due to shared genetic components. The Copine V (CPNE5) gene is involved in Ca(2+) binding and may play an important role in the development of the central nervous system. This study tested the genetic associations of 77 single-nucleotide polymorphisms (SNPs) within the CPNE5 gene with alcohol dependence (AD) and obesity using a Caucasian sample - The Study of Addiction - Genetics and Environment (SAGE) sample (1066 AD cases and 1278 non-AD controls, 422 obese cases and 1395 non-obese controls). The Marshfield sample (1442 obese cases and 2122 non-obese controls) was used for replication of obesity. Multiple logistic regression analysis was performed using the PLINK software. In the SAGE sample, we identified 10 SNPs associated with AD and 17 SNPs associated with obesity (p < 0.05). Interestingly, 6 SNPs (rs9986517, rs9470387, rs3213534, rs10456444, rs3752482, and rs9470386) were associated with both AD (OR = 0.77, 0.77, 0.83, 0.84, 0.79 and 1.14, respectively; p = 9.72 × 10(-5), 1.1 × 10(-4), 4.09 × 10(-3), 5.26 × 10(-3), 1.59 × 10(-2), and 3.81 × 10(-2), respectively) and obesity (OR = 0.77, 0.77, 0.78, 0.77, 0.68 and 1.18, respectively; p = 2.74 × 10(-3), 2.69 × 10(-3), 2.45 × 10(-3), 1.01 × 10(-3), 5.18 × 10(-3) and 3.85 × 10(-2), respectively). In the Marshfield sample, rs3752480 was associated with obesity (p = 0.0379). In addition, four SNPs (rs9986517, rs10456444, rs7763347 and rs4714010) showed associations with obesity in the meta-analysis using both samples (p = 0.00493, 0.0274, 0.00346, and 0.0141, respectively). These findings provide the first evidence of common genetic variants in the CPNE5 gene influencing both the AD and obesity; and will serve as a resource for replication in other populations.
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA. Electronic address: wangk@etsu.edu.
authors.forename: Ke-Sheng
authors.initials: KS
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Changchun
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000150:complications / Q000208:ethnology* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012984:Software; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C000609671:CPNE5 protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins
keywords: Alcohol dependence; CPNE5; Calcium; Haplotype; Meta-analysis; Obesity; Pleiotropic effect; Polymorphism