Sibling Variation in Phenotype and Genotype: Polygenic Trait Distributions and DNA Recombination Mapping with UK Biobank and IVF Family Data

We use UK Biobank and a unique IVF family dataset (including genotyped embryos) to investigate sibling variation in both phenotype and genotype. We compare phenotype (disease status, height, blood biomarkers) and genotype (polygenic scores, polygenic health index) distributions among siblings to those in the general population. As expected, the between-siblings standard deviation in polygenic scores is ![Graphic][1] times smaller than in the general population, but variation is still significant. As previously demonstrated, this allows for substantial benefit from polygenic screening in IVF. Differences in sibling genotypes result from distinct recombination patterns in sexual reproduction. We develop a novel sibling-pair method for detection of recombination breaks via statistical discontinuities. The new method is used to construct a dataset of 1.44 million recombination events which may be useful in further study of meiosis. ### Competing Interest Statement The authors declare the following competing interests: EW and LL are employees and shareholders of Genomic Prediction, Inc. MH is a volunteer (uncompensated) research intern at GP. TGR and MH declare no competing interests. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics IRB of Michigan State University waived ethical approval for this work. It was classified as non-human subjects because we only analyzed genomes with no identifying information. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /embed/inline-graphic-1.gif