From Genotype to Phenotype: polygenic prediction of complex human traits

TL;DR

This paper reviews the current state and future potential of using genomic data to predict complex human traits and diseases, highlighting successes, challenges, and applications across medicine and genetics.

Contribution

It provides a comprehensive overview of polygenic prediction methods, their accuracy, and potential applications in health, embryo selection, and genetic engineering.

Findings

Height and quantitative traits can be predicted with reasonable accuracy.

Individuals with extreme polygenic scores have significantly higher disease risks.

Polygenic scores are validated through sibling comparisons.

Abstract

Decoding the genome confers the capability to predict characteristics of the organism(phenotype) from DNA (genotype). We describe the present status and future prospects of genomic prediction of complex traits in humans. Some highly heritable complex phenotypes such as height and other quantitative traits can already be predicted with reasonable accuracy from DNA alone. For many diseases, including important common conditions such as coronary artery disease, breast cancer, type I and II diabetes, individuals with outlier polygenic scores (e.g., top few percent) have been shown to have 5 or even 10 times higher risk than average. Several psychiatric conditions such as schizophrenia and autism also fall into this category. We discuss related topics such as the genetic architecture of complex traits, sibling validation of polygenic scores, and applications to adult health, in vitro fertilization (embryo selection), and genetic engineering.