Aims and Hypothesis

During the production of lymphoblastoid cell lines for the ALSPAC cohort there has been circumstantial evidence that lymphocytes from some individuals are harder to transform with Epstein Barr Virus than others. Also there is variation in the growth rate of different cultures. The ALSPAC laboratory has collected data on the rate of transformation and rate of growth of cultures once transformed.

We would like to run a GWAS analysis of the cell line characteristics to see if there is a genetic association with transformation success or growth rate of the cultures. In particular we will look to see if genes that have been identified as host genes associated with cancers caused by Epstein Barr Virus are also associted with transformation efficiency. (HLA-A has been shown to be associated with risk of EBV-related Hodgkin lymphoma (Hjalgrim, et al., 2009, Urayama, et al., 2011) and Nasopharyngeal carcinoma (Tse, et al., 2009).

In addition there are phenotypes which could affect the transformation success, for example a recent or past infection with EBV. There are also some reports which suggest that blood pressure ia associated with different cell line growth rates. Therefore we will look to see if there is any association between the cell line characteristics and the infection history, blood pressure and smoking data of the participants the cell lines were obtained from.

Exposure Variables

Smoking, blood pressure and infection history

Outcome Variables

Transformation success rate and growth rate of established cultures

Confounding Variables

Cell counts of original samples, time to processing, original blood volume, age of participant

Karen Ho, ALSPAC cell line RA will provide all the cell line data which can also be incorporated into the main ALSPAC resource. George McMahon has agreed to carry out the GWAS analysis and assist with general statistical analysis.

Any findings could potentially be replicated using data obtained from 1958 birth cohort cell lines subject to approval from the 1958 birth cohort access committee.