Detection of sharing by descent, long-range phasing and haplotype imputation.

Uncertainty about the phase of strings of SNPs creates complications in genetic analysis, although methods have been developed for phasing population-based samples. However, these methods can only phase a small number of SNPs effectively and become unreliable when applied to SNPs spanning many linkage disequilibrium (LD) blocks. Here we show how to phase more than 1,000 SNPs simultaneously for a large fraction of the 35,528 Icelanders genotyped by Illumina chips. Moreover, haplotypes that are identical by descent (IBD) between close and distant relatives, for example, those separated by ten meioses or more, can often be reliably detected. This method is particularly powerful in studies of the inheritance of recurrent mutations and fine-scale recombinations in large sample sets. A further extension of the method allows us to impute long haplotypes for individuals who are not genotyped.

Many sequence variants affecting diversity of adult human height.

Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.