SpringerProtocols: Abstract: Measuring the Effects of Genes and Environment on Complex Traits

Measuring the Effects of Genes and Environment on Complex Traits

By: Jennifer H. Barrett³

Abstract

Full Text

Download PDF (410K)

Complex diseases and traits are influenced by a combination of genetic and environmental risk factors, some of which may be known, and many of which are unknown. It is possible to estimate the relative importance of the influence of genes and environment on a trait by studying correlations in the trait in related individuals. Known risk factors can be measured and included in the statistical models to understand disease etiology better. The joint effect of specific genes and environmental exposures can be estimated by measuring these in individuals, not necessarily related, with and without the disease of interest or with a range of trait values. These methods are illustrated by considering two example analyses in detail. The first is an analysis of a study of adolescent twins, quantifying the effect of genes and environment, including measured sun exposure, on the density of nevi. The second is an analysis of a case-control study, examining the joint effect of the GSTT1 gene and vegetable intake on risk of colorectal cancer.

Affiliation(s): (3) Section of Genetic Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, St James’s University Hospital, Leeds, UK

Book Title: Clinical Bioinformatics

Series: Methods in Molecular Medicine | Volume: 141 | Pub. Date: Dec-21-2007 | Page Range: 55-69 | DOI: 10.1007/978-1-60327-148-6_4

Subject: Bioinformatics

Key Words: genes - environment - complex traits - variance components - gene-environment interaction - twins - case-control study - statistical models

References

Download References

1.	Swerdlow, A. J., English, J., MacKie, R. M., O’Doherty, C. J., Hunter, J. A., Clark, J., et al. (1986) Benign melanocytic naevi as a risk factor for malignant melanoma. Br. Med. J. (Clin Res Ed.) 292, 1555–1559.

2.	Wachsmuth, R. C., Turner, F., Barrett, J. H., Gaut, R., Randerson-Moor, J. A., Bishop, D. T., et al. (2005) The effect of sun exposure in determining nevus density in UK adolescent twins. J. Invest. Dermatol. 124, 56–62.

3.	Wachsmuth, R., Gaut, R., Barrett, J. H., Saunders, C. L., Randerson-Moor, J. A., Eldridge, A., et al. (2001) Heritability and gene–environment interactions for melanocytic nevus density examined in a UK adolescent twin study. J. Invest. Dermatol. 117, 348–352.

4.	Zhu, G., Duffy, D. L., Eldridge, A., Grace, M., Mayne, C., O’Gorman, L., et al. (1999) A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs. Am. J. Hum. Genet. 65, 483–492.

5.	Potter, J. D. (1999) Colorectal cancer: molecules and populations. J. Natl Cancer Inst. 91, 916–932.

6.	Michels, K. B., Edward, G., Joshipura, K. J., Rosner, B. A., Stampfer, M. J., Fuchs, C. S., et al. (2000) Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J. Natl. Cancer Inst. 92, 1740–1752.

7.	Norat, T., Bingham, S., Ferrari, P., Slimani, N., Jenab, M., Mazuir, M., et al. (2005) Meat, fish, and colorectal cancer risk: the european prospective investigation into cancer and nutrition. J. Natl. Cancer Inst. 97, 906–916.

8.	Gallagher, R. P., and McLean, D. I. (1995) The epidemiology of acquired melanocytic nevi. A brief review. Dermatol. Clin. 13, 595–603.

9.	Donner, A. (1986) A review of inference procedures for the intraclass correlation coefficient in the one-way random effects model. Int. Statist. Rev. 54, 67–82.

10.	Sham, P. (1998) Statistics in Human Genetics. Arnold, London, p.242.

11.	Eaves, L. J. (1977) Inferring the causes of human variation. J. Royal Statist. Soc. Series A, 140, 324–355.

12.	English, D. R., Milne, E., and Simpson, J. A. (2006) Ultraviolet radiation at places of residence and the development of melanocytic nevi in children (Australia). Cancer Causes Control 17, 103–107.

13.	Turner, F., Smith, G., Sachse, C., Lightfoot, T., Garner, R. C., Wolf, C. R., et al. (2004) Vegetable, fruit and meat consumption and potential risk modifying genes in relation to colorectal cancer. Int. J. Cancer 112, 259–264.

14.	Wittke-Thompson, J. K., Pluzhnikov, A., and Cox. N. J. (2005) Rational inferences about departures from Hardy–Weinberg equilibrium. Am. J. Hum. Genet. 76, 967–986.

15.	Sachse, C., Smith, G., Wilkie, M., Barrett, J., Waxman, R., Sullivan, F., et al (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23, 1839–1849.

16.	Wacholder, S., Chanock, S., Garcia-Closas, M., El Ghormli, L., and Rothman, N. (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J. Natl. Cancer Inst. 96, 434–442.

Comments (Loading...)

Post comment/View all comments