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Chunk #19 — METHODS — Genetic data analyses

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Heritability and a genome-wide linkage analysis of a Type II/B cluster construct for cannabis dependence in an American Indian community.
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Genotypes were ultimately determined for 416 participants. The total additive genetic variance (heritability, h2) and its standard error were estimated for the CD, ASPD, ASPD/CD phenotypes using SOLAR (http://solar.sfbrgenetics.org/). Two approaches to estimating heritability were used for the three traits. In the first approach the trait was modeled as a latent normally distributed variable with a threshold above which an individual is considered “affected”. Using a second approach, the same trait was modeled as if it was a normally distributed variable. In this case heritability is higher for the trait modeled as if it was a normally distributed variable. These methods can occasionally give very dissimilar results presumably because of factors related to convergence. In this analysis it was required that both methodologies provide support for heritability prior to linkage analyses and the lower estimate is presented. Variance component estimate methods were used to calculate LOD scores using SOLAR v2.0.4 (Almasy & Blangero, 1998). Simulation analysis was used to estimate empirical LOD scores and make appropriate genome wide adjustments for non-normality (Blangero et al. 2000).