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Power consequences of linkage disequilibrium variation between populations.

ABSTRACT: We quantify the degree to which LD differences exist in the human genome and investigates the consequences that variations in patterns of LD between populations can have on the power of case-control or family-trio association studies. Although only a small proportion of SNPs show significant LD differences (0.8-5%), these can introduce artificial signals of associations and reduce the power to detect true associations in case-control designs, even when meta-analytic approaches are used to account for stratification. We show that combining trios from different populations in the presence of significant LD differences can adversely affect power even though the number of trios has increased. Our results have implications on genetic studies conducted in populations with substantial population structure and show that the use of meta-analytic approaches or family-based designs to protect Type 1 error does not prevent loss of power due to differences in LD across populations.

SUBMITTER: Teo YY

PROVIDER: S-EPMC2997478 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Power consequences of linkage disequilibrium variation between populations.

Teo Yik Y YY Small Kerrin S KS Fry Andrew E AE Wu Yumeng Y Kwiatkowski Dominic P DP Clark Taane G TG

Genetic epidemiology 20090201 2

We quantify the degree to which LD differences exist in the human genome and investigates the consequences that variations in patterns of LD between populations can have on the power of case-control or family-trio association studies. Although only a small proportion of SNPs show significant LD differences (0.8-5%), these can introduce artificial signals of associations and reduce the power to detect true associations in case-control designs, even when meta-analytic approaches are used to accoun ...[more]

PMID: 18814308

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Project description:BackgroundThe success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino x Border Leicester), along with an inbred Australian Merino museum flock were analysed.ResultsShort range LD (0 - 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino x Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 - 2.5 centimorgans, depending on the population used.ConclusionSheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.

Dataset Information

Power consequences of linkage disequilibrium variation between populations.

Publications

Power consequences of linkage disequilibrium variation between populations.

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