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

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...

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Vydáno v:American journal of human genetics Ročník 104; číslo 6; s. 1169
Hlavní autoři: 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
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 06.06.2019
Témata:
Adult
Aged
Arthritis, Rheumatoid - epidemiology
Arthritis, Rheumatoid - genetics
Body Mass Index
Colitis, Ulcerative - epidemiology
Colitis, Ulcerative - genetics
Coronary Artery Disease - epidemiology
Coronary Artery Disease - genetics
Crohn Disease - epidemiology
Crohn Disease - genetics
Female
Finland - epidemiology
Genetic Association Studies
Genetic Markers
Genetics, Population
Geography
Humans
Male
Middle Aged
Multifactorial Inheritance - genetics
Polymorphism, Single Nucleotide
Quantitative Trait, Heritable
Risk Factors
Schizophrenia - epidemiology
Schizophrenia - genetics
Waist-Hip Ratio
Finland
genetic prediction
population stratification
genetic structure
ISSN:1537-6605, 1537-6605
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1537-6605
1537-6605
DOI:10.1016/j.ajhg.2019.05.001