Estimation of genetic and environmental factors for melanoma onset using population‐based family data
Abstract
Estimation of genetic and environmental contributions to cancers falls in the framework of generalized linear mixed modelling with several random effect components. Computational challenges remain, however, in dealing with binary or survival phenotypes. In this paper, we consider the analysis of melanoma onset in a population of 2.6 million nuclear families in Sweden, for which none of the current survival‐based methodologies is feasible. We treat the disease outcome as a binary phenotype, so that the standard proportional hazard model leads to a generalized linear model with the complementary‐log link function. For rare diseases this link is very close to the probit link, and thus allows the use of marginal likelihood for the estimation of the variance components. We correct for the survival length bias by censoring the parent generation within each family at the time they attain the same cumulative hazard as the child generation, thus improving the validity of the estimates. Our finding that childhood shared environment in addition to genetic factors had a considerable effect on the development of melanoma is consistent with epidemiological studies. Copyright © 2005 John Wiley & Sons, Ltd.
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The analysis adjusted for birth cohorts, addressing biases due to differences in length of follow-up with study participants in different birth years.
“We adjusted for birth cohorts, addressing biases due to differences in length of follow-up with study participants in different birth years26.”
From The Familial Risk of Autism (2014) · cites this paper as [26]
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- Authors
- Lindström, L., Pawitan, Y., Reilly, M., Hemminki, K., Lichtenstein, P., & Czene, K.
- Affiliations
- Karolinska Institutet (SE)
- German Cancer Research Center (DE)
- Corresponding author
- Czene, K.
- Venue
- Statistics in Medicine
- Publisher
- Wiley
- Published
- 2005-12-22
- Volume
- 25
- Issue
- 18
- Pages
- 3110-3123
- ISSN
- 0277-6715 (ISSN-L)
- 1097-0258
- OpenAlex
- W2165798496
- Cited by
- 9
- References
- 21
- Citations by year
- 2023: 1 · 2020: 1 · 2014: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Statistics in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Keywords
- melanoma, genetic risk factors, environmental risk factors, heritability, nuclear family, generalized linear mixed models, marginal likelihood, variance components, censoring, rare diseases
- MeSH terms
- Adolescent, Adult, Aged, Child, Cocarcinogenesis, Environment, Family, Female, Humans, Male, Melanoma, Middle Aged, Models, Genetic, Pedigree, Sweden, Models, Statistical, Age of Onset, Genetic Predisposition to Disease
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