Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Fast psychomotor functioning in anorexia nervosa: Effect of weight restoration

Item does not contain fulltextIn a previous study young seriously underweight anorexia nervosa (AN) patients in the early phase of treatment were found to react faster in psychomotor tasks. To further understand this finding we studied the impact of weight restoration on the performance of AN patients in drawing and copying tasks. A group of 17 female AN patients, aged 14 to 25, was compared with 17 healthy controls, matched for sex, age and educational level. Patients were tested when severely underweight and after weight restoration. Control subjects were also tested twice. Using computerized recording and analysis of writing and drawing behavior, reaction times and drawing times were derived, while cognitive and motor demands were manipulated. Overall, AN patients showed shorter reaction times in copying tasks and shorter drawing time in the drawing task than normal controls, and this pattern persisted after weight restoration. No significant group (AN vs. controls) by session (test vs. retest) effect emerged. The finding of a consistent pattern of shorter reaction and drawing times in AN patients before and after weight restoration is compatible with a personality characteristic of perfectionism and overachievement in AN patients