Quantitative trait locus (QTL) identification in a Croatian isolate

Lead Research Organisation: MRC Human Genetics Unit

Abstract

The aim of this project is to identify genetic variants influencing susceptibility to common diseases. We are studying a large number of quantitatively varying traits (QTs) (>100 per person) in adult volunteers from isolated communities on the Dalmatian cost of Croatia. These communities have been studied for several decades by our Croatian collaborators. We then carry out whole genome association scans of the DNA samples from each individual using 320,000 genetic markers in order to identify susceptibility genes or regulatory variants. Positive associations are then replicated in other population samples.

Technical Summary

The aims of the study are, firstly, to genetically map and identify quantitative trait loci (QTL) influencing common human traits and disorders in isolated populations.||We have performed whole genome association analyses in samples obtained from an epidemiological field survey of 1,041 individuals from the island of Vis on the Dalmatian coast of Croatia and a similar number from the island of Korcula. Our Croatian collaborators are currently sampling volunteers from the city of Split on the Croatian mainland.||We propose to replicate and fine map the most significant QTL in other isolate and general population samples. Once this has been achieved, QTL will be identified by further genotyping and direct sequencing of candidate genes within each identified region.||In addition, we propose to estimate the genetic parameters and analyse the distributions of the >100 quantitative traits (QTs) analysed to date.||We are currently extending the field work by analysing further QTs (total of approximately 100) and harmonising the methods and choice of QTs with other members of the EUROSPAN FP6 consortium of isolate populations (Sweden, Netherlands, Croatia, Scotland, Italy). ||We have carried out a 320,000 single nucleotide polymorphism (SNP) whole genome scan in 2,000 members from the Croatian isolate, to carry out a QT genetic association study.

Publications

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Böger CA (2011) CUBN is a gene locus for albuminuria. in Journal of the American Society of Nephrology : JASN

 
Description CHARGE 
Organisation Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE)
Country Global 
Sector Academic/University 
PI Contribution Contributed to mamt international GWAS meta-analyses
Collaborator Contribution Many publications in high impact journals
Impact Many publications in high impact journals
Start Year 2009
 
Description CROATIAN cohorts 
Organisation University of Split
Country Croatia 
Sector Academic/University 
PI Contribution Contributed to the setting up and collection of samples as well as overseeing the analysis of genotype data
Collaborator Contribution Allowed the advancement of studying the genetics of isolated populations.
Impact Many publications. Funding obtained for expansion of this collaboration.
 
Description GIANT 
Organisation Broad Institute
Department The Genetic Investigation of ANthropometric Traits (GIANT)
Country United States 
Sector Academic/University 
PI Contribution Contributed to many analyses related to anthropometric measures
Collaborator Contribution Contributed to many meta-analyses
Impact Many publications in high impact journals
Start Year 2009
 
Description MAGIC 
Organisation Broad Institute
Department The Genetic Investigation of ANthropometric Traits (GIANT)
Country United States 
Sector Academic/University 
PI Contribution Contributed to meta-analysis of metabolic syndrome related traits
Collaborator Contribution Contributed to several meta-analyses.
Impact Several publications in high impact journals
Start Year 2009
 
Description SPIROMETA 
Organisation SpiroMeta Consortium
Country Global 
Sector Academic/University 
PI Contribution Contributed to meta-analyses of lung function related traits
Collaborator Contribution Many publications in high impact journals
Impact Several publications in high impact journals
Start Year 2009
 
Title MODY biomarker (PCT/EP2011/067112) 
Description Biomarker distinguishing MODY from T2D 
IP Reference WO2012042020 
Protection Patent granted
Year Protection Granted 2012
Licensed No
Impact None as yet