caa a22 4500 445376252 CHVBK 20180317143003.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00702-011-0628-3 doi (NATIONALLICENCE)springer-10.1007/s00702-011-0628-3 Family-based association analysis of alcohol dependence in the COGA sample and replication in the Australian twin-family study [Elektronische Daten] [Ke-Sheng Wang, Xuefeng Liu, Nagesh Aragam, Xueqiu Jian, Jerald Mullersman, Yali Liu, Yue Pan] Family, twin, and adoption studies have indicated that genetic and environmental factors contribute to the development of alcohol dependence (AD). We conducted a low-density genome-wide association analysis to identify genetic variants influencing AD. We used 11,120 SNPs from the Affymetrix 10K Genechips genotyped in 116 Caucasian pedigrees (272 nuclear families) from Genetic Analysis Workshop 14, a subset from the Collaborative Study on the Genetics of Alcoholism (COGA). Family-based association analyses for AD were performed by the PBAT program for autosomal SNPs and by the FBAT program for X-chromosome SNPs. We identified 37 SNPs associated with AD (P<10−3), thirteen of which were located in known genes. The most significant association with AD was observed with SNP rs1986644 (P=8.51×10−6) at 13q22 near EDNRB gene. The next best signal was at 1q41 in USH2A (rs532342, P=1.07×10−5) and the third region was at 3q25.31 in TIPARP (rs1367311, P=2.31×10−5). Furthermore, we found support for association of MAOA gene (P=4.14×10−4 for rs979606). Six of the 37 AD associated SNPs were confirmed to be associated with AD in Australian twin-family study sample (P<0.05). Interestingly, four SNPs in DSCAML1 at 11q23 reached the genome-wide significance (the top SNP is rs10892169 with P=5.31×10−9), while rs637547 in NKAIN2 at 6q21 showed strong association with AD (P=5.11×10−7) in the replication sample. These findings offer the potential for new insights into the pathogenesis of AD and will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in AD. Springer-Verlag, 2011 Alcohol dependence nationallicence Family-based association nationallicence DSCAML1 nationallicence MAOA nationallicence TIPARP nationallicence USH2A nationallicence Wang Ke-Sheng Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut Liu Xuefeng Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut Aragam Nagesh Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut Jian Xueqiu Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut Mullersman Jerald Department of Pathology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA aut Liu Yali Department of Mathematics and Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, TN, USA aut Pan Yue Department of Mathematics and Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, TN, USA aut Journal of Neural Transmission Springer Vienna 118/9(2011-09-01), 1293-1299 0300-9564 118:9<1293 2011 118 702 https://doi.org/10.1007/s00702-011-0628-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-011-0628-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Ke-Sheng Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut NATIONALLICENCE 700 1- Liu Xuefeng Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut NATIONALLICENCE 700 1- Aragam Nagesh Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut NATIONALLICENCE 700 1- Jian Xueqiu Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Lamb Hall, PO Box 70259, 37614-1700, Johnson City, TN, USA aut NATIONALLICENCE 700 1- Mullersman Jerald Department of Pathology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA aut NATIONALLICENCE 700 1- Liu Yali Department of Mathematics and Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, TN, USA aut NATIONALLICENCE 700 1- Pan Yue Department of Mathematics and Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, TN, USA aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/9(2011-09-01), 1293-1299 0300-9564 118:9<1293 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer