Rxivist logo

Geographic variation and bias in polygenic scores of complex diseases and traits in Finland

By Sini Kerminen, Alicia R. Martin, Jukka Koskela, Sanni E Ruotsalainen, Aki S. Havulinna, Ida Surakka, Aarno Palotie, Markus Perola, Veikko Salomaa, Mark J. Daly, Samuli Ripatti, Matti Pirinen

Posted 04 Dec 2018
bioRxiv DOI: 10.1101/485441 (published DOI: 10.1016/j.ajhg.2019.05.001)

Polygenic scores (PS) are becoming a useful tool to identify individuals with high genetic risk for complex diseases and several projects are currently testing their utility for translational applications. It is also tempting to use PS to assess whether genetic variation can explain a part of the geographic distribution of a phenotype. However, it is not well known how population genetic properties of the training and target samples affect the geographic distribution of PS. Here, we evaluate geographic differences, and related biases, of PS in Finland with geographically well-defined sample of 2,376 individuals from the National FINRISK study. First, we detect geographic differences in PS for coronary artery disease (CAD), rheumatoid arthritis, schizophrenia, waits-hip ratio (WHR), body-mass index (BMI) and height, but not for Crohn's disease or ulcerative colitis. Second, we use height as a model trait to thoroughly assess the possible population genetic biases in PS and apply similar approaches to the other phenotypes. Most importantly, we detect suspiciously large accumulation of geographic differences for CAD, WHR, BMI and height, suggesting bias arising from population genetic structure rather than from a direct genotype-phenotype association. This work demonstrates how sensitive the geographic patterns of current PS are for small biases even within relatively homogenous populations and provides simple tools to identify such biases. A thorough understanding of the effects of population genetic structure on PS is essential for translational applications of PS.

Download data

  • Downloaded 1,002 times
  • Download rankings, all-time:
    • Site-wide: 16,989 out of 118,130
    • In genetics: 891 out of 5,131
  • Year to date:
    • Site-wide: 66,020 out of 118,130
  • Since beginning of last month:
    • Site-wide: 64,952 out of 118,130

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News