Imputing Phenotypes for Genome-wide Association Studies

Farhad Hormozdiari, Eun Yong Kang, Michael Bilow, Eyal Ben-David, Chris Vulpe, Stela McLachlan, Aldons J. Lusis, Buhm Han*, Eleazar Eskin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageAmerican English
Pages (from-to)89-103
Number of pages15
JournalAmerican Journal of Human Genetics
Issue number1
StatePublished - 7 Jul 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 American Society of Human Genetics


Dive into the research topics of 'Imputing Phenotypes for Genome-wide Association Studies'. Together they form a unique fingerprint.

Cite this