Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Design and analysis of association studies using pooled DNA from large twin samples
AU - Knight, Jo
AU - Sham, Pak
PY - 2006/9
Y1 - 2006/9
N2 - Evidence is mounting that multiple genes are involved in complex traits and that these each account for very small proportions of the overall phenotypic variance. Association studies of many markers in 1000s of individuals will be required to identify such genes. A number of large twin cohorts have already been collected and provide a valuable resource for carrying out studies that are robust to the effect of population stratification. Technologies based on microarrays will soon allow 1.000,000 SNPs to be typed at one time, however financial considerations prevent most researchers from using these approaches to genotype all individuals. Recently, microarrays have been shown to give accurate allele frequency measurements in pooled DNA samples and provide a simple way to select the best markers for individual genotyping. This drastically reduces the cost and workload of large scale association studies. One limitation of this methodology relates to the analytical procedures which have only been developed to allow comparison of two pools e.g. case/control pools. In this paper we use meta-regression to analyze pooled DNA data allowing the allele frequency in each pool to be related to the average quantitative phenotypic measure of the individuals whose DNA were used to construct the pools. Alongside this we describe a technique that can be used to determine the power for such studies. We present results from some preliminary investigations of different pooling strategies that can be applied to large twin samples and demonstrate that the method retains a large proportion of the power available from individual genotyping.
AB - Evidence is mounting that multiple genes are involved in complex traits and that these each account for very small proportions of the overall phenotypic variance. Association studies of many markers in 1000s of individuals will be required to identify such genes. A number of large twin cohorts have already been collected and provide a valuable resource for carrying out studies that are robust to the effect of population stratification. Technologies based on microarrays will soon allow 1.000,000 SNPs to be typed at one time, however financial considerations prevent most researchers from using these approaches to genotype all individuals. Recently, microarrays have been shown to give accurate allele frequency measurements in pooled DNA samples and provide a simple way to select the best markers for individual genotyping. This drastically reduces the cost and workload of large scale association studies. One limitation of this methodology relates to the analytical procedures which have only been developed to allow comparison of two pools e.g. case/control pools. In this paper we use meta-regression to analyze pooled DNA data allowing the allele frequency in each pool to be related to the average quantitative phenotypic measure of the individuals whose DNA were used to construct the pools. Alongside this we describe a technique that can be used to determine the power for such studies. We present results from some preliminary investigations of different pooling strategies that can be applied to large twin samples and demonstrate that the method retains a large proportion of the power available from individual genotyping.
KW - Computer Simulation
KW - DNA
KW - Gene Frequency
KW - Humans
KW - Meta-Analysis as Topic
KW - Models, Genetic
KW - Models, Theoretical
KW - Regression Analysis
KW - Reproducibility of Results
KW - Twin Studies as Topic
KW - Twins
U2 - 10.1007/s10519-005-9016-9
DO - 10.1007/s10519-005-9016-9
M3 - Journal article
C2 - 16479323
VL - 36
SP - 665
EP - 677
JO - Behavior Genetics
JF - Behavior Genetics
SN - 0001-8244
IS - 5
ER -