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1.  Genome-wide association studies: potential next steps on a genetic journey 
Human Molecular Genetics  2008;17(R2):R156-R165.
Genome-wide association studies have successfully identified numerous loci at which common variants influence disease risk or quantitative traits. Despite these successes, the variants identified by these studies have generally explained only a small fraction of the heritable component of disease risk, and have not pinpointed with certainty the causal variant(s) at the associated loci. Furthermore, the mechanisms of action by which associated loci influence disease or quantitative phenotypes are often unclear, because we do not know through which gene(s) the associated variants exert their effects or because these gene(s) are of unknown function or have no clear connection to known disease biology. Thus, the initial set of genome-wide association studies serve as a starting point for future genetic and functional studies. We outline possible next steps that may help accelerate progress from genetic studies to the biological knowledge that can guide the development of predictive, preventive, or therapeutic measures.
PMCID: PMC2782356  PMID: 18852205
2.  Dissection of the genetics of Parkinson's disease identifies an additional association 5′ of SNCA and multiple associated haplotypes at 17q21 
Human Molecular Genetics  2010;20(2):345-353.
We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P< 10−4). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P< 10−10) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.
PMCID: PMC3005904  PMID: 21044948
3.  European lactase persistence genotype shows evidence of association with increase in body mass index 
Human Molecular Genetics  2009;19(6):1129-1136.
The global prevalence of obesity has increased significantly in recent decades, mainly due to excess calorie intake and increasingly sedentary lifestyle. Here, we test the association between obesity measured by body mass index (BMI) and one of the best-known genetic variants showing strong selective pressure: the functional variant in the cis-regulatory element of the lactase gene. We tested this variant since it is presumed to provide nutritional advantage in specific physical and cultural environments. We genetically defined lactase persistence (LP) in 31 720 individuals from eight European population-based studies and one family study by genotyping or imputing the European LP variant (rs4988235). We performed a meta-analysis by pooling the β-coefficient estimates of the relationship between rs4988235 and BMI from the nine studies and found that the carriers of the allele responsible for LP among Europeans showed higher BMI (P = 7.9 × 10−5). Since this locus has been shown to be prone to population stratification, we paid special attention to reveal any population substructure which might be responsible for the association signal. The best evidence of exclusion of stratification came from the Dutch family sample which is robust for stratification. In this study, we highlight issues in model selection in the genome-wide association studies and problems in imputation of these special genomic regions.
PMCID: PMC2830824  PMID: 20015952

Results 1-3 (3)