Case-control studies with affected sibships

Related cases may be included in case-control association studies if correlations between related individuals due to identity-by-descent (IBD) sharing are taken into account. We derived a framework to test for association in a case-control design including affected sibships and unrelated controls. First, a corrected variance for the allele frequency difference between cases and controls was directly calculated or estimated in two ways on the basis of the fixation index FST and the inbreeding coefficient. Then the correlation-corrected association test including controls and affected sibs was carried out. We applied the three strategies to 20 candidate genes on the Genetic Analysis Workshop 15 rheumatoid arthritis data and to 9187 single-nucleotide polymorphisms of replicate one of the Genetic Analysis Workshop 15 simulated data with knowledge of the "answers". The three strategies used to correct for correlation give only minor differences in the variance estimates and yield an almost correct type I error rate for the association tests. Thus, all strategies considered to correct the variance performed quite well

Nonparametric longitudinal allele-sharing model

Basically no methods are available for the analysis of quantitative traits in longitudinal genetic epidemiological studies. We introduce a nonparametric factorial design for longitudinal data on independent sib pairs, modelling the phenotypic quadratic differences as the dependent variable. Factors are the number of alleles shared identically by descent (IBD) and the age categories at which the dependent variable is measured, allowing for dependence due to age. To identify a linked marker a rank statistic tests the influence of IBD group on phenotypic quadratic differences. No assumptions are made on normality or variances of the dependent variable. We apply our method to 71 sib pairs from the Framingham Heart Study data provided at the Genetic Analysis Workshop 13. For all 15 available markers on chromosome 17 we analyzed the influence on systolic blood pressure. In addition, different selection strategies to sample from the whole data are discussed

Surrogate phenotype definition for alcohol use disorders: a genome-wide search for linkage and association

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

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements