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Chunk #14 — METHODS — Molecular Methods and Analysis — Linkage samples and analyses

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Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.
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Non-parametric, multipoint methods of linkage analysis for affected sibling pairs were employed, first using the microsatellite linkage panel, and subsequently with the SNP linkage panel, using the program ASPEX (Hinds & Risch, 1999). The linkage analyses were performed using only those affected siblings with both parents genotyped (sib_ibd), which allows unambiguous estimation of IBD. This type of analysis results in greater accuracy in the estimate of marker allele sharing among affected siblings. Analyses were performed using all possible pairs of affected siblings [n(n − 1)/2), where n = number of affected siblings in a nuclear family]. First, each of the phenotypes (alcohol dependence, conduct disorder, and suicide attempts) was analyzed individually, parallel to the previous reports (however, we note that the results are slightly different than the original publications, reflecting an updated genetic map). Subsequently, all three phenotypes were combined, such that affected status was defined by the presence of alcohol dependence (AD) or conduct disorder (CD) or suicide attempts (SUI). Finally, an analysis focused on only the subset of alcohol-dependent individuals who also have either conduct disorder or a suicide attempt (AD with CD or SUI) was conducted.