Dataset Information

Estimating sibling spillover effects with unobserved confounding using gain-scores.

ABSTRACT:

Purpose

A growing area of research in epidemiology is the identification of health-related sibling spillover effects, or the effect of one individual's exposure on their sibling's outcome. The health within families may be confounded by unobserved factors, rendering identification of sibling spillovers challenging.

Methods

We demonstrate a gain-score (fixed effects) regression method for identifying exposure-to-outcome spillover effects within sibling pairs in linear models. The method identifies the exposure-to-outcome spillover effect if only one sibling's exposure affects the other's outcome, and it identifies the difference between the spillover effects if both siblings' exposures affect the others' outcomes. The method fails with outcome-to-exposure spillover or with outcome-to-outcome spillover. Analytic results, Monte Carlo simulations, and a brief application demonstrate the method and its limitations.

Results

We estimate the spillover effect of a child's preterm birth on an older sibling's literacy skills, measured by the Phonological Awareness Literacy Screening-Kindergarten test. We analyze 20,010 sibling pairs from a population-wide, Wisconsin-based (United States) birth cohort. Without covariate adjustment, we estimate that preterm birth modestly decreases an older sibling's test score.

Conclusions

Gain-scores are a promising strategy for identifying exposure-to-outcome spillover effects in sibling pairs while controlling for sibling-invariant unobserved confounding.

SUBMITTER: Mallinson DC

PROVIDER: S-EPMC8960330 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Estimating sibling spillover effects with unobserved confounding using gain-scores.

Mallinson David C DC Elwert Felix F

Annals of epidemiology 20220103

<h4>Purpose</h4>A growing area of research in epidemiology is the identification of health-related sibling spillover effects, or the effect of one individual's exposure on their sibling's outcome. The health within families may be confounded by unobserved factors, rendering identification of sibling spillovers challenging.<h4>Methods</h4>We demonstrate a gain-score (fixed effects) regression method for identifying exposure-to-outcome spillover effects within sibling pairs in linear models. The m ...[more]

PMID: 34990828

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Project description:BackgroundControlling unobserved confounding still remains a great challenge in observational studies, and a series of strict assumptions of the existing methods usually may be violated in practice. Therefore, it is urgent to put forward a novel method.MethodsWe are interested in the causal effect of an exposure on the outcome, which is always confounded by unobserved confounding. We show that, the causal effect of an exposure on a continuous or categorical outcome is nonparametrically identified through only two independent or correlated available confounders satisfying a non-linear condition on the exposure. Asymptotic theory and variance estimators are developed for each case. We also discuss an extension for more than two binary confounders.ResultsThe simulations show better estimation performance by our approach in contrast to the traditional regression approach adjusting for observed confounders. A real application is separately applied to assess the effects of Body Mass Index (BMI) on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Fasting Blood Glucose (FBG), Triglyceride (TG), Total Cholesterol (TC), High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL) with individuals in Shandong Province, China. Our results suggest that SBP increased 1.60 (95% CI: 0.99-2.93) mmol/L with per 1- kg/m2 higher BMI and DBP increased 0.37 (95% CI: 0.03-0.76) mmol/L with per 1- kg/m2 higher BMI. Moreover, 1- kg/m2 increase in BMI was causally associated with a 1.61 (95% CI: 0.96-2.97) mmol/L increase in TC, a 1.66 (95% CI: 0.91-55.30) mmol/L increase in TG and a 2.01 (95% CI: 1.09-4.31) mmol/L increase in LDL. However, BMI was not causally associated with HDL with effect value - 0.20 (95% CI: - 1.71-1.44). And, the effect value of FBG per 1- kg/m2 higher BMI was 0.56 (95% CI: - 0.24-2.18).ConclusionsWe propose a novel method to control unobserved confounders through double binary confounders satisfying a non-linear condition on the exposure which is easy to access.

Project description:Indirect parental genetic effects may be defined as the influence of parental genotypes on offspring phenotypes over and above that which results from the transmission of genes from parents to their children. However, given the relative paucity of large-scale family-based cohorts around the world, it is difficult to demonstrate parental genetic effects on human traits, particularly at individual loci. In this manuscript, we illustrate how parental genetic effects on offspring phenotypes, including late onset conditions, can be estimated at individual loci in principle using large-scale genome-wide association study (GWAS) data, even in the absence of parental genotypes. Our strategy involves creating "virtual" mothers and fathers by estimating the genotypic dosages of parental genotypes using physically genotyped data from relative pairs. We then utilize the expected dosages of the parents, and the actual genotypes of the offspring relative pairs, to perform conditional genetic association analyses to obtain asymptotically unbiased estimates of maternal, paternal and offspring genetic effects. We apply our approach to 19066 sibling pairs from the UK Biobank and show that a polygenic score consisting of imputed parental educational attainment SNP dosages is strongly related to offspring educational attainment even after correcting for offspring genotype at the same loci. We develop a freely available web application that quantifies the power of our approach using closed form asymptotic solutions. We implement our methods in a user-friendly software package IMPISH (IMputing Parental genotypes In Siblings and Half Siblings) which allows users to quickly and efficiently impute parental genotypes across the genome in large genome-wide datasets, and then use these estimated dosages in downstream linear mixed model association analyses. We conclude that imputing parental genotypes from relative pairs may provide a useful adjunct to existing large-scale genetic studies of parents and their offspring.

Dataset Information

Estimating sibling spillover effects with unobserved confounding using gain-scores.

Purpose

Methods

Results

Conclusions

Publications

Estimating sibling spillover effects with unobserved confounding using gain-scores.

Similar Datasets

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