European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Concurrent Symposia 12
S33. Genomics of bipolar affective: from multiply affected
families to the general population
M. Nöthen;
Department of Genomics, University of Bonn, Bonn, Germany.
Bipolar affective disorder (BPAD) is characterized by severe episodes
of mania and depression and represents a common disorder affecting
approximately 1% of the world’s population. Therefore, BPAD is
considered to be one of the top public health problems associated with
a significant morbidity. Although formal genetic studies consistently
provide strong evidence for a major genetic contribution to BPAD, the
underlying genetic architecture is poorly understood.
Using family samples from different European populations we implicated
several chromosomal regions in the development of BPAD, including
regions on chromosomes 1, 4, 6, 8, and 10 (e.g. Cichon et
al. Hum Mol Genet 2001, Schumacher et al. Am J Hum Genet 2005).
A genome-wide interaction linkage scan provided strong interaction
evidence between BPAD genes on chromosomes 2q22-q24 and 6q23q24,
and 2q22-q24 and 15q26. Focusing on specific candidate genes,
the best evidence was obtained for G72/G30 and tryptophan hydoxylase
2 (e.g. Schulze et al Am J Psychiatry 2006). The recent first
genome-wide association study was a further progress in the genetic
study of BPAD showing that several genes, each of modest effect, reproducibly
influence disease risk (Baumer et al. Mol Psychiatry 2007).
Specifically, the gene DGKH showed significant association even after
conservative experiment-wise correction.
The causative mutations in the implicated genes for BPAD, however,
remain to be identified. As soon as these will be known, samples of
patients collected from the general population will allow estimation of
parameters such as relative risks and etiological fraction.
S34. Large population studies
W. E. R. Ollier;
Centre for Integrated Genomic Medical Research, University of Manchester,
Manchester, United Kingdom.
Approaches in Genetic Epidemiology have now advanced technically
to such as extent that it is increasingly possible to capture longitudinal
real-time clinical phenotype and exposure data relating to massive
population samples. When this is combined with relentless advances
in high-throughput and low-cost technologies to define either laboratory-based
phenotypes/biomarkers or genetic/transcriptomic profiles,
vast meta-databases are being generated. Analysis and mining of
such multi-level datasets will reveal important insights into the health
and disease at both a population and individual level. This will particularly
relate to disease progression, and gene-environment interactions
relating to drugs (pharmacogenetics) and nutrients (nutrigenomics).
Such longitudinal population-based cohort studies are now being
developed in a range of countries, taking advantage of advances in
health service infrastructure for electronic clinical record capture. UK
Biobank (www.ukbiobank.ac.uk) is such a study, designed to investigate
both health and disease in the UK.
At the same time, large national and international collections of samples
and data are being assembled for case-control studies of specific
diseases (www.dna-network.ac.uk), www.genomeutwin.org). These
are being used in whole genome association studies using high density
genotyping (>500,000 SNP loci). Examples of such projects include
the WTCCC (www.wtccc.org.uk) and GAIN (www.fnih.org/GAIN/
GAIN_home.shtml).
Such massive initiatives are required to generate the levels of power
and replication studies to detect small genotype relative risks (