Improper Adjustment for Baseline in Genetic Association Studies of Change in Phenotype

Overview

Journal Hum Hered

Specialty Genetics

Date 2008 Dec 17

PMID 19077436

Citations 7

Authors

P F McArdle

B W Whitcomb

Affiliations

Soon will be listed here.

Abstract

Objective: In studies of associations between genetic factors and outcomes where change in phenotype is of interest, proper modeling of the data, particularly the treatment of baseline trait values, is required to draw valid conclusions.

Methods: The authors compared models of blood pressure response to a cold pressor test with and without inclusion of baseline blood pressure as a regressor and evaluate the resultant biases.

Results: Adjustment for baseline presents a potential source of bias for assessment of genotype-phenotype associations. This bias was observed to occur both under the absence of a true effect, as well when a relation between genotype and change in phenotype was simulated. In simulations that incorporated measurement error, estimates were as great as two fold the true parameter values when unmeasured confounding was a factor.

Conclusions: Adjusting for baseline introduces bias in genetic association studies when change in phenotype is the outcome of interest. Model misspecification bias may impact inference and provide one possible source of non-replication of findings in the literature.

Citing Articles

A statistical perspective on baseline adjustment in pharmacogenomic genome-wide association studies of quantitative change.

Zhang H, Chhibber A, Shaw P, Mehrotra D, Shen J NPJ Genom Med. 2022; 7(1):33.

PMID: 35680959 PMC: 9184591. DOI: 10.1038/s41525-022-00303-2.

The impact of adjusting for baseline in pharmacogenomic genome-wide association studies of quantitative change.

Oni-Orisan A, Haldar T, Ranatunga D, Medina M, Schaefer C, Krauss R NPJ Genom Med. 2020; 5:1.

PMID: 31969989 PMC: 6965183. DOI: 10.1038/s41525-019-0109-4.

Impact of home visit capacity on genetic association studies of late-onset Alzheimer's disease.

Fardo D, Gibbons L, Mukherjee S, Glymour M, McCormick W, McCurry S Alzheimers Dement. 2017; 13(8):933-939.

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Should Studies of Diabetes Treatment Stratification Correct for Baseline HbA1c?.

Jones A, Lonergan M, Henley W, Pearson E, Hattersley A, Shields B PLoS One. 2016; 11(4):e0152428.

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Unbalanced baseline in school-based interventions to prevent obesity: adjustment can lead to bias - a systematic review.

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