Genetic Evidence that Humans Have Pushed Orang-utans to the Brink of Extinction

For the identification of susceptibility loci in complex diseases the choice of the target phenotype is very important. We compared results of genome-wide searches for linkage or for association related to three phenotypes for alcohol use disorder. These are a behavioral score BQ, based on a 12-item questionnaire about drinking behavior and the subject's report of drinking-related health problems, and ERP pattern and ERP magnitude, both derived from the eyes closed resting ERP measures to quantify brain activity. Overall, we were able to identify 11 candidate regions for linkage. Only two regions were found to be related to both BQ and one of the ERP phenotypes. The genome-wide search for association using single-nucleotide polymorphisms did not yield interesting leads. Background For the identification of susceptibility loci in complex diseases, genome-wide searches are a first step. Study design issues such as sample structure and marker choice play a role. However, of fundamental importance is a precise, homogeneous, and insightful phenotype definition. The right hunch might be the key to a particular disease pathway. The Genetic Analysis Workshop 14 (GAW14) family data on alcohol use disorders (short: alcoholism) provide the possibility to compose new phenotypes for alcoholism. These are either based on 12 questions regarding drinking behavior and the subject's report of drinkingrelated health problems or on eyes closed resting eventrelated potential (ERP) measures to quantify brain activity, possibly defining a phenotype closer to a biological pathway. To localize susceptibility regions for alcoholism we first separately construct one phenotype for drinking behavior and two for ERP measures, pattern (P) and magnitude (M), taking clustering within families into account. Genetic information is not used in this step. Previous studies of ERP focused on the amplitudes of measurements. However, the pattern of measures can be more important than the magnitude (e.g., LDL:HDL ratio, CD4:CD8 ratio of lymphocytes). For ERP we considered both the pattern of an individual's ERP measurements and the magnitude (amplitude). Secondly, we performed a genome-wide linkage search with microsatellite markers and an association search with single-nucleotide polymorphisms (SNPs). Then we compared the results yielded by the different phenotypes and searches. Methods General phenotype construction Behavioral questions (BQ) and ERP measures are multidimensional. We employed a reduction to a single score from Genetic Analysis Workshop 14: Microsatellite and single-nucleotide polymorphism Noordwijkerhout, The Netherlands, 7-10 September 2004 Published: 30 December 2005 BMC Genetics 2005, 6(Suppl 1):S55 doi:10.1186/1471-2156-6-S1-S55 Genetic Analysis Workshop 14: Microsatellite and single-nucleotide polymorphism Joan E Bailey-Wilson, Laura Almasy, Mariza de Andrade, Julia Bailey, Heike Bickeböller, Heather J Cordell, E Warwick Daw, Lynn Goldin, Ellen L Goode, Courtney GrayMcGuire, Wayne H ning, ail Jarvik, Brion S Maher, Nancy Mendell, Andrew D Paterson, John Rice, Glen Satten, Brian Suar z, Veronica Vieland, Marsha Wilcox, Heping Zhang, Andre s Ziegler and Jean W MacCluer Proceedings