Comment | Published:

The illusion of polygenic disease risk prediction

A problem at the interface of genomic medicine and medical screening is that genetic associations of etiological significance are often interpreted as having predictive significance. Genome-wide association studies (GWAS) have identified many thousands of associations between common DNA variants and hundreds of diseases and benign traits. This knowledge has generated many publications with the understandable expectation that it can be used to derive polygenic risk scores for predicting disease to identify those at sufficiently high risk to benefit from preventive intervention. However, the expectation rests on the incorrect assumption that odds ratios derived from polygenic risk scores that are important etiologically are also directly useful in risk prediction and population screening.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    Khera AV, Chaffin M, Aragam KG et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50:1219–1224.

  2. 2.

    Inouye M, Abraham G, Nelson CP, Wood AM, Sweeting MJ, Dudbridge F et al. Genomic risk prediction of coronary artery disease in 280,000 adults: Implications for primary prevention. J Am Coll Cardiol 2018;72.

  3. 3.

    Wald NJ, Hackshaw AK, Frost CD. When can a risk factor be used as a worthwhile screening test? BMJ. 1999;319:1562–1565.

  4. 4.

    Wald NJ, Morris JK. Assessing risk factors as potential screening tests: a simple assessment tool. Arch Intern Med. 2011;171:286–291.

  5. 5.

    Schumacher FR, Al Olama AA, Berndt SI, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet. 2018;50:928–936.

  6. 6.

    Khoury MJ, Janssens AC, Ransohoff DF. How can polygenic inheritance be used in population screening for common diseases? Genet Med. 2013;15:437–443.

  7. 7.

    Chowdhury S, Dent T, Pashayan N, et al. Incorporating genomics into breast and prostate cancer screening: assessing the implications. Genet Med. 2013;15:423–432.

Download references

Author information


The authors declare no conflicts of interest.

Correspondence to Nicholas J. Wald FRS.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Further reading

Fig. 1