Genetic structure is detectable based on religious background in this study of Newfoundland and Labrador. That could be a consequence of marrying someone with the same religion, even though the general geographic background might not be that different. http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg2015256a.html Genetic structure of the Newfoundland and Labrador population: founder effects modulate variability. Zhai G(1), Zhou J(2), Woods MO(1), Green JS(1), Parfrey P(2), Rahman P(2), Green RC(1). Author information: (1)Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada. (2)Discipline of Medicine, Faculty of Medicine, Memorial University, St John's, Newfoundland and Labrador, Canada. The population of the province of Newfoundland and Labrador (NL) has been a resource for genetic studies because of its historical isolation and increased prevalence of several monogenic disorders. Controversy remains regarding the genetic substructure and the extent of genetic homogeneity, which have implications for disease gene mapping. Population substructure has been reported from other isolated populations such as Iceland, Finland and Sardinia. We undertook this study to further our understanding of the genetic architecture of the NL population. We enrolled 494 individuals randomly selected from NL. Genome-wide SNP data were analyzed together with that from 14 other populations including HapMap3, Ireland, Britain and Native American samples from the Human Genome Diversity Project. Using multidimensional scaling and admixture analysis, we observed that the genetic structure of the NL population resembles that of the British population but can be divided into three clusters that correspond to religious/ethnic origins: Protestant English, Roman Catholic Irish and North American aboriginals. We observed reduced heterozygosity and an increased inbreeding coefficient (mean=0.005), which corresponds to that expected in the offspring of third-cousin marriages. We also found that the NL population has a significantly higher number of runs of homozygosity (ROH) and longer lengths of ROH segments. These results are consistent with our understanding of the population history and indicate that the NL population may be ideal for identifying recessive variants for complex diseases that affect populations of European origin.European Journal of Human Genetics advance online publication, 16 December 2015; doi:10.1038/ejhg.2015.256.