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The limits of normal approximation for adult height.

ABSTRACT: 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.

SUBMITTER: Slavskii SA

PROVIDER: S-EPMC8298501 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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The limits of normal approximation for adult height.

Slavskii Sergei A SA Kuznetsov Ivan A IA Shashkova Tatiana I TI Bazykin Georgii A GA Axenovich Tatiana I TI Kondrashov Fyodor A FA Aulchenko Yurii S YS

European journal of human genetics : EJHG 20210304 7

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 insuffici ...[more]

PMID: 33664501

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Project description:PurposeTo establish age-related, normal limits of monocular and binocular spatial vision under photopic and mesopic conditions.MethodsPhotopic and mesopic visual acuity (VA) and contrast thresholds (CTs) were measured with both positive and negative contrast optotypes under binocular and monocular viewing conditions using the Acuity-Plus (AP) test. The experiments were carried out on participants (age range from 10 to 86 years), who met pre-established, normal sight criteria. Mean and ± 2.5σ limits were calculated within each 5-year subgroup. A biologically meaningful model was then fitted to predict mean values and upper and lower threshold limits for VA and CT as a function of age. The best-fit model parameters describe normal aging of spatial vision for each of the 16 experimental conditions investigated.ResultsOut of the 382 participants recruited for this study, 285 participants passed the selection criteria for normal aging. Log transforms were applied to ensure approximate normal distributions. Outliers were also removed for each of the 16 stimulus conditions investigated based on the ±2.5σ limit criterion. VA, CTs and the overall variability were found to be age-invariant up to ~50 years in the photopic condition. A lower, age-invariant limit of ~30 years was more appropriate for the mesopic range with a gradual, but accelerating increase in both mean thresholds and intersubject variability above this age. Binocular thresholds were smaller and much less variable when compared to the thresholds measured in either eye. Results with negative contrast optotypes were significantly better than the corresponding results measured with positive contrast (p < 0.004).ConclusionsThis project has established the expected age limits of spatial vision for monocular and binocular viewing under photopic and high mesopic lighting with both positive and negative contrast optotypes using a single test, which can be implemented either in the clinic or in an occupational setting.

Dataset Information

The limits of normal approximation for adult height.

Publications

The limits of normal approximation for adult height.

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