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
Ameur A
(2012)
Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids.
in American journal of human genetics
Aulchenko YS
(2009)
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
in Nature genetics
Bakija-Konsuo A
(2011)
Leprosy epidemics during history increased protective allele frequency of PARK2/PACRG genes in the population of the Mljet Island, Croatia.
in European journal of medical genetics
Barbalic M
(2009)
A quantitative trait locus for SBP maps near KCNB1 and PTGIS in a population isolate.
in American journal of hypertension
Biloglav Z
(2009)
Historic, demographic, and genetic evidence for increased population frequencies of CCR5Delta32 mutation in Croatian Island isolates after lethal 15th century epidemics.
in Croatian medical journal
Boraska V
(2012)
Genome-wide meta-analysis of common variant differences between men and women.
in Human molecular genetics
Böger CA
(2011)
CUBN is a gene locus for albuminuria.
in Journal of the American Society of Nephrology : JASN
Cabrera CP
(2012)
Uncovering networks from genome-wide association studies via circular genomic permutation.
in G3 (Bethesda, Md.)
| 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 | GLYSCOSYLATION MARKERS FOR THE DIAGNOSIS OF MATURITY ONSET DIABETES OF THE YOUNG |
| Description | A method for diagnosing Maturity-Onset Diabetes of the Young (MODY) in a subject is provided. The method comprises providing a glycan- containing test sample from the subject; determining one or more levels of fucosylation of the glycans in the test sample; comparing the one or more levels of fucosylation with one or more reference values; and providing a diagnosis based on said comparison. This method may be used to distinguish HNF1A-MODY or HNF4A-MODY from other types of diabetes such that the correct treatment may be prescribed for the subject. |
| IP Reference | WO2012042020 |
| Protection | Patent granted |
| Year Protection Granted | 2012 |
| Licensed | No |
| Impact | None as yet |