Imputing Phenotypes for Genome-wide Association Studies.
Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the s...
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ftcdlib:oai:escholarship.org:ark:/13030/qt5vp0c3kw 2023-06-11T04:15:20+02:00 Imputing Phenotypes for Genome-wide Association Studies. Hormozdiari, Farhad Kang, Eun Yong Bilow, Michael Ben-David, Eyal Vulpe, Chris McLachlan, Stela Lusis, Aldons J Han, Buhm Eskin, Eleazar 89 - 103 2016-07-01 application/pdf https://escholarship.org/uc/item/5vp0c3kw unknown eScholarship, University of California qt5vp0c3kw https://escholarship.org/uc/item/5vp0c3kw public American journal of human genetics, vol 99, iss 1 Animals Humans Mice Triglycerides Body Mass Index Cohort Studies Reproducibility of Results Sample Size Blood Pressure Genotype Multifactorial Inheritance Phenotype Models Genetic Research Design Finland Genome-Wide Association Study Datasets as Topic Prevention Genetics Cardiovascular Bioengineering Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity article 2016 ftcdlib 2023-05-08T17:56:29Z Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be insufficient to achieve the desired statistical power. The phenotype of interest is often difficult to collect, whereas surrogate phenotypes or related phenotypes are easier to collect and have already been collected in very large samples. This paper demonstrates how we take advantage of these additional related phenotypes to impute the phenotype of interest or target phenotype and then perform association analysis. Our approach leverages the correlation structure between phenotypes to perform the imputation. The correlation structure can be estimated from a smaller complete dataset for which both the target and related phenotypes have been collected. Under some assumptions, the statistical power can be computed analytically given the correlation structure of the phenotypes used in imputation. In addition, our method can impute the summary statistic of the target phenotype as a weighted linear combination of the summary statistics of related phenotypes. Thus, our method is applicable to datasets for which we have access only to summary statistics and not to the raw genotypes. We illustrate our approach by analyzing associated loci to triglycerides (TGs), body mass index (BMI), and systolic blood pressure (SBP) in the Northern Finland Birth Cohort dataset. Article in Journal/Newspaper Northern Finland University of California: eScholarship |
institution |
Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Animals Humans Mice Triglycerides Body Mass Index Cohort Studies Reproducibility of Results Sample Size Blood Pressure Genotype Multifactorial Inheritance Phenotype Models Genetic Research Design Finland Genome-Wide Association Study Datasets as Topic Prevention Genetics Cardiovascular Bioengineering Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity |
spellingShingle |
Animals Humans Mice Triglycerides Body Mass Index Cohort Studies Reproducibility of Results Sample Size Blood Pressure Genotype Multifactorial Inheritance Phenotype Models Genetic Research Design Finland Genome-Wide Association Study Datasets as Topic Prevention Genetics Cardiovascular Bioengineering Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity Hormozdiari, Farhad Kang, Eun Yong Bilow, Michael Ben-David, Eyal Vulpe, Chris McLachlan, Stela Lusis, Aldons J Han, Buhm Eskin, Eleazar Imputing Phenotypes for Genome-wide Association Studies. |
topic_facet |
Animals Humans Mice Triglycerides Body Mass Index Cohort Studies Reproducibility of Results Sample Size Blood Pressure Genotype Multifactorial Inheritance Phenotype Models Genetic Research Design Finland Genome-Wide Association Study Datasets as Topic Prevention Genetics Cardiovascular Bioengineering Human Genome Biological Sciences Medical and Health Sciences Genetics & Heredity |
description |
Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be insufficient to achieve the desired statistical power. The phenotype of interest is often difficult to collect, whereas surrogate phenotypes or related phenotypes are easier to collect and have already been collected in very large samples. This paper demonstrates how we take advantage of these additional related phenotypes to impute the phenotype of interest or target phenotype and then perform association analysis. Our approach leverages the correlation structure between phenotypes to perform the imputation. The correlation structure can be estimated from a smaller complete dataset for which both the target and related phenotypes have been collected. Under some assumptions, the statistical power can be computed analytically given the correlation structure of the phenotypes used in imputation. In addition, our method can impute the summary statistic of the target phenotype as a weighted linear combination of the summary statistics of related phenotypes. Thus, our method is applicable to datasets for which we have access only to summary statistics and not to the raw genotypes. We illustrate our approach by analyzing associated loci to triglycerides (TGs), body mass index (BMI), and systolic blood pressure (SBP) in the Northern Finland Birth Cohort dataset. |
format |
Article in Journal/Newspaper |
author |
Hormozdiari, Farhad Kang, Eun Yong Bilow, Michael Ben-David, Eyal Vulpe, Chris McLachlan, Stela Lusis, Aldons J Han, Buhm Eskin, Eleazar |
author_facet |
Hormozdiari, Farhad Kang, Eun Yong Bilow, Michael Ben-David, Eyal Vulpe, Chris McLachlan, Stela Lusis, Aldons J Han, Buhm Eskin, Eleazar |
author_sort |
Hormozdiari, Farhad |
title |
Imputing Phenotypes for Genome-wide Association Studies. |
title_short |
Imputing Phenotypes for Genome-wide Association Studies. |
title_full |
Imputing Phenotypes for Genome-wide Association Studies. |
title_fullStr |
Imputing Phenotypes for Genome-wide Association Studies. |
title_full_unstemmed |
Imputing Phenotypes for Genome-wide Association Studies. |
title_sort |
imputing phenotypes for genome-wide association studies. |
publisher |
eScholarship, University of California |
publishDate |
2016 |
url |
https://escholarship.org/uc/item/5vp0c3kw |
op_coverage |
89 - 103 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
American journal of human genetics, vol 99, iss 1 |
op_relation |
qt5vp0c3kw https://escholarship.org/uc/item/5vp0c3kw |
op_rights |
public |
_version_ |
1768372051730497536 |