- Email: [email protected]
The integration of genetic data into epidemiological longitudinal studies
Abstracts / Toxicology 226 (2006) 12–77
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that only a limited number of events are necessary to generate a tumour. This bodes well for prevention and treatment.
The integration of genetic data into epidemiological longitudinal studies
References
Imperial College, London, UK
Hickman, J.A., 2002. Curr. Opin. Genetics Dev. 12, 67–72. Lowe, S.W., Cepero, E., Evan, G., 2004. Nature 432, 307315. Levine, B., Yuan, J., 2005. J. Clin. Invest. 115, 2679–2688.
doi:10.1016/j.tox.2006.05.019 The writing life of James D. Watson: Writing The Double Helix Errol C. Friedberg Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 753909072, USA E-mail address: [email protected] James (Jim) Watson is of course best known for the co-discovery (with the late Francis Crick) of the structure of DNA and for his seminal contributions to the Human Genome Project. Less well known is his prolific contribution to literature, notably his several biographical books (The Double Helix and Genes, Girls and Gamow, his numerous essays (some of which are presented in A Passion For DNA) and commentaries (The DNA Story), and the several textbooks (Molecular Biology of the Gene, Molecular Biology of the Cell and Recombinant DNA) that he either co-authored or orchestrated in some way. This talk will primarily consider events that transpired during and immediately following the writing of The Double Helix, events that are at least as interesting and controversial as the famous story told in that book. Further reading Friedberg, E.C., 2005. The Writing Life of James D. Watson. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, New York.
doi:10.1016/j.tox.2006.05.020
Paolo Vineis
A seminal paper by Lewontin (1972) drew the attention of researchers on the mistakes involved in partitioning nature and nurture. Many investigations on gene-environment interactions (GEI) are under way in different parts of the world, a subject that also appears as one of the leading items in grant calls from NIH or EU. Some on-going studies are extremely large (e.g. EPIC, UK Biobank). In addition, newer technologies, such as proteomics, metabolomics and gene expression are already in use or will be soon tested within such large studies. There is a tendency to standardize laboratory methods (at least for genotyping), while exposure assessment is extremely variable, being for example state-of–the-art for dietary intake in some studies, but not in other studies or for other exposures. GEI imply studying both environmental exposures (e.g. to pesticides or environmental tobacco smoke) and genetic variants that are supposed to modulate the effects of the former. However, there is an asymmetry between the two. Genotyping is in fact much more accurate than the vast majority of methods used to measure environmental exposures. This implies a lower degree of classification error that in turn means an easier identification of associations with disease. A further difficulty is related to the rarity of many environmental exposures (that, however, may have an important impact on human health), while several of the polymorphic alleles that are investigated are common. This, again, increases the probability of detecting an association with genotypes (if this is real), but not with environmental exposures. These and other methodological issues related to the investigation of GEI in large epidemiological studies will be addressed. doi:10.1016/j.tox.2006.05.021
13
that only a limited number of events are necessary to generate a tumour. This bodes well for prevention and treatment.
The integration of genetic data into epidemiological longitudinal studies
References
Imperial College, London, UK
Hickman, J.A., 2002. Curr. Opin. Genetics Dev. 12, 67–72. Lowe, S.W., Cepero, E., Evan, G., 2004. Nature 432, 307315. Levine, B., Yuan, J., 2005. J. Clin. Invest. 115, 2679–2688.
doi:10.1016/j.tox.2006.05.019 The writing life of James D. Watson: Writing The Double Helix Errol C. Friedberg Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 753909072, USA E-mail address: [email protected] James (Jim) Watson is of course best known for the co-discovery (with the late Francis Crick) of the structure of DNA and for his seminal contributions to the Human Genome Project. Less well known is his prolific contribution to literature, notably his several biographical books (The Double Helix and Genes, Girls and Gamow, his numerous essays (some of which are presented in A Passion For DNA) and commentaries (The DNA Story), and the several textbooks (Molecular Biology of the Gene, Molecular Biology of the Cell and Recombinant DNA) that he either co-authored or orchestrated in some way. This talk will primarily consider events that transpired during and immediately following the writing of The Double Helix, events that are at least as interesting and controversial as the famous story told in that book. Further reading Friedberg, E.C., 2005. The Writing Life of James D. Watson. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, New York.
doi:10.1016/j.tox.2006.05.020
Paolo Vineis
A seminal paper by Lewontin (1972) drew the attention of researchers on the mistakes involved in partitioning nature and nurture. Many investigations on gene-environment interactions (GEI) are under way in different parts of the world, a subject that also appears as one of the leading items in grant calls from NIH or EU. Some on-going studies are extremely large (e.g. EPIC, UK Biobank). In addition, newer technologies, such as proteomics, metabolomics and gene expression are already in use or will be soon tested within such large studies. There is a tendency to standardize laboratory methods (at least for genotyping), while exposure assessment is extremely variable, being for example state-of–the-art for dietary intake in some studies, but not in other studies or for other exposures. GEI imply studying both environmental exposures (e.g. to pesticides or environmental tobacco smoke) and genetic variants that are supposed to modulate the effects of the former. However, there is an asymmetry between the two. Genotyping is in fact much more accurate than the vast majority of methods used to measure environmental exposures. This implies a lower degree of classification error that in turn means an easier identification of associations with disease. A further difficulty is related to the rarity of many environmental exposures (that, however, may have an important impact on human health), while several of the polymorphic alleles that are investigated are common. This, again, increases the probability of detecting an association with genotypes (if this is real), but not with environmental exposures. These and other methodological issues related to the investigation of GEI in large epidemiological studies will be addressed. doi:10.1016/j.tox.2006.05.021