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

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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 .

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 organization: Institute for Molecular Medicine Finland
Helsinki Institute of Life Science HiLIFE
Samuli Olli Ripatti / Principal Investigator
Centre of Excellence in Complex Disease Genetics
Aarno Palotie / Principal Investigator
Department of Public Health
Biostatistics Helsinki
Helsinki Institute for Information Technology
Department of Mathematics and Statistics
Complex Disease Genetics
Genomics of Neurological and Neuropsychiatric Disorders
Statistical and population genetics
Date: 2019-06-06
Language: eng
Number of pages: 13
Belongs to series: American Journal of Human Genetics
ISSN: 0002-9297
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.
1184 Genetics, developmental biology, physiology
3124 Neurology and psychiatry
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: draft

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