Abstract
There is an increasing recognition of the potential role of variants in mitochondrial DNA and nuclear-encoded mitochondrial proteins in modifying disease risk. This has led to a rise in the number of mitochondrial association studies being undertaken. The unique inheritance pattern of mitochondria makes mitochondrial DNA variation susceptible to having geographical structure. Such a structure may have a dramatic impact on mitochondrial association studies, particularly in heterogeneous populations. By combining self-reported ancestry data and mitochondrial genotype data for a sample of 3839 individuals from 1037 Australian families, population substructure is tested by looking for evidence of differences in mitochondrial haplogroup and single nucleotide polymorphism (SNP) frequencies between different ancestral groups in Australia. In addition, the substructure within ancestral groups is tested by comparing the similarity of mates to randomly drawn pairs of individuals from the same ancestral group. It is shown that there are significant differences in the frequency of variants both between European and non-European groups, and within Europe. This agrees with previous studies of European mitochondrial variation. No evidence was found for structure within ancestral groups. These results have implications for future association studies in the Australian population, and other populations of heterogeneous ancestry.
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Acknowledgements
We are grateful to the twins and their families for their generous participation in these studies. We thank Ann Eldridge and Marlene Grace for the collection of data and Megan Campbell and Anjali Henders for managing sample processing and preparation, and Brian McEvoy for helpful comments and suggestions. Financial support was provided by grants from the National Health and Medical Research Council (241944, 389875 and 389892). EB is supported by University of Queensland IPRS and UQILAS Awards, GWM and PMV are supported by NHMRC Research Fellowships and AFM is supported by NHMRC Postdoctoral Fellowship no. 496719.
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Byrne, E., McRae, A., Zhao, ZZ. et al. The use of common mitochondrial variants to detect and characterise population structure in the Australian population: implications for genome-wide association studies. Eur J Hum Genet 16, 1396–1403 (2008). https://doi.org/10.1038/ejhg.2008.117
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DOI: https://doi.org/10.1038/ejhg.2008.117
