title: Bivariate genome-wide association analyses identified genetic pleiotropic effects for bone mineral density and alcohol drinking in Caucasians.
abstract: Several studies indicated bone mineral density (BMD) and alcohol intake might share common genetic factors. The study aimed to explore potential SNPs/genes related to both phenotypes in US Caucasians at the genome-wide level. A bivariate genome-wide association study (GWAS) was performed in 2069 unrelated participants. Regular drinking was graded as 1, 2, 3, 4, 5, or 6, representing drinking alcohol never, less than once, once or twice, three to six times, seven to ten times, or more than ten times per week respectively. Hip, spine, and whole body BMDs were measured. The bivariate GWAS was conducted on the basis of a bivariate linear regression model. Sex-stratified association analyses were performed in the male and female subgroups. In males, the most significant association signal was detected in SNP rs685395 in DYNC2H1 with bivariate spine BMD and alcohol drinking (P = 1.94 × 10-8). SNP rs685395 and five other SNPs, rs657752, rs614902, rs682851, rs626330, and rs689295, located in the same haplotype block in DYNC2H1 were the top ten most significant SNPs in the bivariate GWAS in males. Additionally, two SNPs in GRIK4 in males and three SNPs in OPRM1 in females were suggestively associated with BMDs (of the hip, spine, and whole body) and alcohol drinking. Nine SNPs in IL1RN were only suggestively associated with female whole body BMD and alcohol drinking. Our study indicated that DYNC2H1 may contribute to the genetic mechanisms of both spine BMD and alcohol drinking in male Caucasians. Moreover, our study suggested potential pleiotropic roles of OPRM1 and IL1RN in females and GRIK4 in males underlying variation of both BMD and alcohol drinking.
authors.affiliation: Key Lab of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St.Suite 2001, New Orleans, LA, 70112, USA.
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Key Lab of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China.
authors.forename: Xiang-Ding
authors.initials: XD
authors.lastname: Chen
authors.affiliation: School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.affiliation: Key Lab of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China.
authors.forename: Ke-Hao
authors.initials: KH
authors.lastname: Wu
authors.affiliation: Key Lab of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Tan
authors.affiliation: Key Lab of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China.
authors.forename: Zhuo-Er
authors.initials: ZE
authors.lastname: Wang
authors.affiliation: Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, China.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Pei
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St.Suite 2001, New Orleans, LA, 70112, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Key Lab of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, China. hdeng2@tulane.edu.|Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, China. hdeng2@tulane.edu.|Center for Bioinformatics and Genomics, Department of Biostatistics, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St.Suite 2001, New Orleans, LA, 70112, USA. hdeng2@tulane.edu.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D005260:Female; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics*
keywords: Alcohol drinking; Bivariate genome-wide association study; Bone mineral density; DYNC2H1