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Direct genetic effects and their estimation from matched case-control data

(2012) GENETIC EPIDEMIOLOGY. 36(6). p.652-662
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Bioinformatics: from nucleotids to networks (N2N)
Abstract
In genetic association studies, a single marker is often associated with multiple, correlated phenotypes (e.g., obesity and cardiovascular disease, or nicotine dependence and lung cancer). A pervasive question is then whether that marker exerts independent effects on all phenotypes. In this paper, we address this question by assessing whether there is a genetic effect on one phenotype that is not mediated through the other ones, so called direct genetic effect. Answering such question may represent an important step in the elucidation of the underlying biological mechanism. Under rather restrictive conditions, such direct genetic effects are known to be estimable by standard regression methods. Under more lenient conditions, in a prospective or unmatched case-control study, these effects can be estimated by using a previously proposed G-estimation method (Vansteelandt [2009] Epidemiology 20, 851860). The present paper extends this method to matched case-control studies, and investigates the conditions under which this extension is valid. We illustrate the method on data from a matched case-control study, which we use to elucidate the pathway implications of a detected association between myocardial infarction and a genetic locus in the chromosomal region of the FTO gene.
Keywords
GENOME-WIDE ASSOCIATION, SENSITIVITY-ANALYSIS, G-estimation, causal diagram, FTO GENE, ADULT OBESITY, VARIANTS, MODELS, COMMON, INDEPENDENCE, INFERENCE, BIAS, mediation, genetic pathway

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Citation

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Chicago
Berzuini, Carlo, Stijn Vansteelandt, Luisa Foco, Roberta Pastorino, and Luisa Bernardinelli. 2012. “Direct Genetic Effects and Their Estimation from Matched Case-control Data.” Genetic Epidemiology 36 (6): 652–662.
APA
Berzuini, C., Vansteelandt, S., Foco, L., Pastorino, R., & Bernardinelli, L. (2012). Direct genetic effects and their estimation from matched case-control data. GENETIC EPIDEMIOLOGY, 36(6), 652–662.
Vancouver
1.
Berzuini C, Vansteelandt S, Foco L, Pastorino R, Bernardinelli L. Direct genetic effects and their estimation from matched case-control data. GENETIC EPIDEMIOLOGY. 2012;36(6):652–62.
MLA
Berzuini, Carlo, Stijn Vansteelandt, Luisa Foco, et al. “Direct Genetic Effects and Their Estimation from Matched Case-control Data.” GENETIC EPIDEMIOLOGY 36.6 (2012): 652–662. Print.
@article{3167747,
  abstract     = {In genetic association studies, a single marker is often associated with multiple, correlated phenotypes (e.g., obesity and cardiovascular disease, or nicotine dependence and lung cancer). A pervasive question is then whether that marker exerts independent effects on all phenotypes. In this paper, we address this question by assessing whether there is a genetic effect on one phenotype that is not mediated through the other ones, so called direct genetic effect. Answering such question may represent an important step in the elucidation of the underlying biological mechanism. Under rather restrictive conditions, such direct genetic effects are known to be estimable by standard regression methods. Under more lenient conditions, in a prospective or unmatched case-control study, these effects can be estimated by using a previously proposed G-estimation method (Vansteelandt [2009] Epidemiology 20, 851860). The present paper extends this method to matched case-control studies, and investigates the conditions under which this extension is valid. We illustrate the method on data from a matched case-control study, which we use to elucidate the pathway implications of a detected association between myocardial infarction and a genetic locus in the chromosomal region of the FTO gene.},
  author       = {Berzuini, Carlo and Vansteelandt, Stijn and Foco, Luisa and Pastorino, Roberta and Bernardinelli, Luisa},
  issn         = {0741-0395},
  journal      = {GENETIC EPIDEMIOLOGY},
  language     = {eng},
  number       = {6},
  pages        = {652--662},
  title        = {Direct genetic effects and their estimation from matched case-control data},
  url          = {http://dx.doi.org/10.1002/gepi.21660},
  volume       = {36},
  year         = {2012},
}

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