Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates

To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR) and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum Body Mass Index (BMI), concern over mistakes (CM) and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals

The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs

<p>Abstract</p> <p>Understanding the nature of evolutionary relationships among persons and populations is important for the efficient application of genome science to biomedical research. We have analysed 8,525 autosomal single nucleotide polymorphisms (SNPs) in 84 individuals from four populations: African-American, European-American, Chinese and Japanese. Individual relationships were reconstructed using the allele sharing distance and the neighbour-joining tree making method. Trees show clear clustering according to population, with the root branching from the African-American clade. The African-American cluster is much less star-like than European-American and East Asian clusters, primarily because of admixture. Furthermore, on the East Asian branch, all ten Chinese individuals cluster together and all ten Japanese individuals cluster together. Using positional information, we demonstrate strong correlations between inter-marker distance and both locus-specific F_ST(the proportion of total variation due to differentiation) levels and branch lengths. Chromosomal maps of the distribution of locus-specific branch lengths were constructed by combining these data with other published SNP markers (total of 33,704 SNPs). These maps clearly illustrate a non-uniform distribution of human genetic substructure, an instructional and useful paradigm for education and research.</p