Monthly Area 1 Teleconference
Transdisciplinary Research in Cancer of the Lung (TRICL)
August 14, 2012
Participants: Heike Bickeboller, Chris Amos, Teri Landi, Thorunn Rafnar, Darren
Brenner, Mala Pande, Michelle Hildebrandt, Maria Timofeeva, Paul Brennan
Action items from last time. Fine mapping studies need to be done quickly. Rayjean
was transferring information about regions for further study to Yufei. This activity
needs to be completed as quickly as possible.
Agenda Items
.1. Genotype selection (Amos, Pande)
Chris created a spreadsheet that lists all the elections. People need to send SNPs
and genes and should tell everybody what they’ve sent for Chris. Chris will confirm
what you’ve sent so if you don’t hear from him and you sent something let him
know.
Chris will send out a prioritization strategy for SNP selection (done). This has been
reviewed and will be posted to the website.
Highest priority is for SNPs and genes defined from our meta-analysis.
Heike suggested choosing SNPs from other diseases. Chris said these would receive
lower priority than lung cancer or other genes relating to GAME-ON initiatives.
However, a general call for more precise inclusion of top SNPs related to
inflammation was suggested. SNPs relating to European ancestry are needed to
control for European ancestry since one of the regions of interest is the HLA region.
Chris sent the list of SNPs for evaluation to Mike Seldin for his comment and has
received feedback that the Exome array includes a large number of European
Ancestry and Continental Ancestry SNPs. A list of about 1200 additional European
Ancestry SNPs has been provided by Mike Seldin and included in the list of SNPs
for transmission to Affymetrix.
Chris will send SNPs out to everybody and Darren will convene a group to look at
them (done).
Chris got a list of genes from James, and it was clarified that these were derived
from analysis of TCGA data (lung cancer germ line sequencing data) for genetic
susceptibiility.
Analyses from other GAME-ON studies are ongoing. SNP selection for a GAME-ON
chip are expected to be requested by the end of this year so we will need to proceed
very quickly with our genotyping to be ready for this next call for SNPs.
Dial in information for Affymetrix call Thursday at 10:30 CDT, Aug 16, 2012.
2. Selection of studies for replication analysis (Hung)
Meeting in July went well. Talked about what populations to phenotype in the next
phase. Priority will be given to cohort studies. Once we do cohort studies – not a lot
of space left for case-control studies. Rayjean Hung needs to circulate the list of
populations that are being selected for study and the prioritization scheme we have
developed.
3. Development of Game-On chip (Amos)
We do not have the meeting minutes from the GAME-ON July yet.
GAME-ON is planning to deploy a consortium wide array. We all will
proceed with developing an array that encompasses all of the groups.
Some groups are further along. Our results should be available by the end
of the year. At the meeting there was discussion about how much money
each group has to contribute. We can do more genotyping at lower cost if
we pool our money across the consortium. We’ll meet at the ASHG
meetings and will start having conference calls at the end of August.
Prices have come down for genotyping.
4. Pathway analyses (Bickeboller)
Melanie has finished her dissertation and moved to another job. A copy of
her dissertation will be provided to TRICL when it is completed. A
manuscript has been completed. A second paper describing geneenvironment interaction has been completed and the group is still waiting
for some revisions. A complete manuscript kernel based methods of
pathway analysis and has been rejected from American Journal of Human
Genetics and will submit elsewhere.
5. Hierarchical analyses (Hung)
A manuscript has been completed and sent to Human Genetics. Should
hear back in a few weeks. Work presented in Milan is complete. Hope to
have a draft manuscript by the end of the month.
6. Further development of statistical methods for meta-analysis (Rosenberger)
Dr. Rosenberger was not available.
7. Gene x environment analysis (Amos)
Dr. Amos has sent a script to Rayjean. Don’t know the status. A paper
was published on methods of Human Heredity.
8. Report from U19 meeting (comments from Amos, Hung, Bickeboller, Landi,
Risch)
There was considerable discussion about potential for a renewal as well as
development of a GAME-ON chip and deliverables. TRICL needs to
deposit findings from the GWAS on dbGAP and then results from pan
GAME-ON analyses will also be published on dbGAP, starting with a
HapMap 2 analysis, followed by a 1000 Genomes analysis.
9. Updates on meta-analysis using HapMap 2 and 1000 genomes
Its been hard to get a protocol from GAME-On for best practices in
imputation for 1000 Genomes. Therefore, TRICL should adopts its own
strategy and proceed from that. At M.D. Anderson Cancer Center
imputations are finished for HapMap 2 and 1000 genomes but association
studies are not finished. Currently HapMap 2 based imputation is missing
for some of the GWAS in the consortium. For consistency with GAME-ON
it is suggested to perform imputation from HapMap 2 first and then
provide to the rest of the consortium. We can also do an analysis from 1000
Genomes and write a paper without waiting for them. A query was sent to
individual GWAS to report status of imputation and analysis (on-going
item).
Update on transition of grant (Amos)
Grant had been approved for renewal but MD Anderson has not
relinquished the grant to Dartmouth yet. If the grant is not relinquished
soon then there may be problems with processing funding. MD Anderson
says it will decide within a week. There is no concern with uploading data
on MDACC server. We have configured the server at Dartmouth.
Next call: September 11, 2012 @ 10-11 EDT