TY - JOUR

T1 - The limits of normal approximation for adult height

AU - Slavskii, Sergei A.

AU - Kuznetsov, Ivan A.

AU - Shashkova, Tatiana I.

AU - Bazykin, Georgii A.

AU - Axenovich, Tatiana I.

AU - Kondrashov, Fyodor A.

AU - Aulchenko, Yurii S.

N1 - Publisher Copyright: © 2021, The Author(s).

PY - 2021/7

Y1 - 2021/7

N2 - Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait.

AB - Adult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait.

UR - http://www.scopus.com/inward/record.url?scp=85112120965&partnerID=8YFLogxK

U2 - 10.1038/s41431-021-00836-7

DO - 10.1038/s41431-021-00836-7

M3 - Article

C2 - 33664501

AN - SCOPUS:85112120965

VL - 29

SP - 1082

EP - 1091

JO - European journal of human genetics

JF - European journal of human genetics

SN - 1018-4813

IS - 7

ER -