Geographic Variation and Bias in the Polygenic Scores of Complex Diseases and Traits in Finland

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http://hdl.handle.net/10138/312886

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Kerminen , S , Martin , A R , Koskela , J , Ruotsalainen , S E , Havulinna , A S , Surakka , I , Palotie , A , Perola , M , Salomaa , V , Daly , M J , Ripatti , S & Pirinen , M 2019 , ' Geographic Variation and Bias in the Polygenic Scores of Complex Diseases and Traits in Finland ' , American Journal of Human Genetics , vol. 104 , no. 6 , pp. 1169-1181 . https://doi.org/10.1016/j.ajhg.2019.05.001

Title: Geographic Variation and Bias in the Polygenic Scores of Complex Diseases and Traits in Finland
Author: Kerminen, Sini; Martin, Alicia R.; Koskela, Jukka; Ruotsalainen, Sanni E.; Havulinna, Aki S.; Surakka, Ida; Palotie, Aarno; Perola, Markus; Salomaa, Veikko; Daly, Mark J.; Ripatti, Samuli; Pirinen, Matti
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2019-06-06
Language: eng
Number of pages: 13
Belongs to series: American Journal of Human Genetics
ISSN: 0002-9297
URI: http://hdl.handle.net/10138/312886
Abstract: Polygenic scores (PSs) 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 PSs to assess whether genetic variation can explain a part of the geographic distribution of a phenotype. However, it is not well known how the population genetic properties of the training and target samples affect the geographic distribution of PSs. Here, we evaluate geographic differences, and related biases, of PSs in Finland in a geographically well-defined sample of 2,376 individuals from the National FINRISK study. First, we detect geographic differences in PSs for coronary artery disease (CAD), rheumatoid arthritis, schizophrenia, waist-hip ratio (WHR), body-mass index (BMI), and height, but not for Crohn disease or ulcerative colitis. Second, we use height as a model trait to thoroughly assess the possible population genetic biases in PSs and apply similar approaches to the other phenotypes. Most importantly, we detect suspiciously large accumulations of geographic differences for CAD, WHR, BMI, and height, suggesting bias arising from the population's genetic structure rather than from a direct genotype-phenotype association. This work demonstrates how sensitive the geographic patterns of current PSs are for small biases even within relatively homogeneous populations and provides simple tools to identify such biases. A thorough understanding of the effects of population genetic structure on PSs is essential for translational applications of PSs.
Subject: INFLAMMATORY-BOWEL-DISEASE
GENETIC ARCHITECTURE
SCHIZOPHRENIA
RISK
LOCI
METAANALYSIS
PREDICTION
DISORDERS
INSIGHTS
BIOLOGY
1184 Genetics, developmental biology, physiology
3124 Neurology and psychiatry
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