Journal
NATURE HUMAN BEHAVIOUR
Volume 5, Issue 12, Pages 1744-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41562-021-01119-3
Keywords
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Funding
- SSGAC
- Pershing Square Fund of the Foundations of Human Behavior
- Ragnar Soderberg Foundation [E42/15]
- ERC [647648]
- Open Philanthropy [010623-00001]
- Riksbankens Jubileumsfond [P18-0782:1]
- Swedish Research Council [2019-00244, 421-2013-1061]
- NIA/NIH [R24-AG065184, R01-AG042568, R56-AG058726, K99-AG062787-01]
- NIH/NICHD [R01-HD083613, R01-HD092548]
- NIA/NIMH [R01-MH101244-02, U01-MH109539-02]
- Netherlands Organisation for Scientific Research VENI [016.Veni.198.058]
- Government of Canada through Genome Canada
- Ontario Genomics Institute [OGI-152]
- Social Sciences and Humanities Research Council of Canada
- European Union [MP1GI18418R]
- Estonian Research Council [PRG1291]
- National Health and Medical Research Council [GNT113400]
- Australian Research Council
- European Research Council (ERC) [647648] Funding Source: European Research Council (ERC)
- Swedish Research Council [2019-00244] Funding Source: Swedish Research Council
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This study introduces the concept and construction methods of polygenic indexes, providing a theoretical framework and an estimator to aid in interpreting and improving their accuracy in analyses.
Benjamin et al. construct polygenic indexes (DNA-based predictors) for 47 phenotypes and make them available to researchers in 11 datasets. They also present a theoretical framework and estimator to help interpret analyses using polygenic indexes. Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.
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