Patterns of linkage disequilibrium of LRRK2 across different races: implications for genetic association studies

PLoS One. 2013 Sep 5;8(9):e75041. doi: 10.1371/journal.pone.0075041. eCollection 2013.

Abstract

Genome Wide Association Studies (GWASs) have identified trait-associated polymorphisms via a hypothesis-free approach. However, it is challenging when attempting to reproduce GWAS findings in different populations as it fundamentally relies on the similar patterns of linkage disequilibrium (LD) between the unknown causal variants and the genotyped single nucleotide polymorphisms (SNPs). To address this potential limitation, we examined the regional LD pattern of leucine-rich repeat kinase 2 (LRRK2) gene, which is responsible for both autosomal dominant and sporadic Parkinson's disease (PD), in Caucasians (CEU), Japanese (JPT) and Chinese (CHB) from HapMap and Chinese (CHS), Malays (MAS) and Indians (INS) from the Singapore Genome Variation Project (SGVP) utilizing the traditional heatmaps and targeted analysis of LRRK2 gene via Monte Carlo simulation through varLD scores of these ethnic groups. Both heatmaps and targeted analysis showed that LD pattern of JPT was different from that of INS (P=0.0001); while LD pattern of CEU was different from that in Asian except for INS (all P=0.0001). Our study suggests that there is a higher chance to detect associations between PD and those trait-associated SNPs of LRRK2 gene found in Caucasian studies in INS, while those found in Japanese studies are likely to be better replicated among CHB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People / genetics
  • Databases, Genetic
  • Ethnicity
  • Gene Frequency
  • Genes, Dominant
  • Genetic Association Studies*
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Linkage Disequilibrium*
  • Monte Carlo Method
  • Parkinson Disease / ethnology*
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Singapore
  • White People

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases

Grants and funding

This study was supported by National Medical Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.