title: Patterns of linkage disequilibrium at PARK16 may explain variances in genetic association studies.
abstract: BACKGROUND
  Reproducing genomewide association studies findings in different populations is challenging, because the reproducibility fundamentally relies on the similar patterns of linkage disequilibrium between the unknown causal variants and the genotyped single-nucleotide polymorphisms (SNPs).
  
  
  METHODS
  The PARK16 locus was reported to alter the risk of Parkinson's disease (PD) in genomewide association studies in Japanese and Caucasians. We evaluated the regional linkage disequilibrium pattern at PARK16 locus in Caucasians, Japanese, and Chinese from HapMap and Chinese, Malays, and Indians from the Singapore Genome Variation Project, using the traditional heatmaps and targeted analysis of PARK16 gene via Monte Carlo simulation through varLD scores of these ethnic groups.
  
  
  RESULTS
  One hundred SNPs in Caucasians, 95 SNPs in Chinese, 78 SNPs in Japanese from HapMap, 86 SNPs in Chinese, 99 SNPs in Indians, and 97 SNPs in Malays from the Singapore Genome Variation Project were included. Our targeted analysis showed that the linkage disequilibrium pattern of SNPs close to rs947211 was similar in Caucasians and Asians, including Chinese, Japanese, and Malay (all P > 0.0001), whereas different linkage disequilibrium patterns around rs823128, rs823156, and rs708730 were found between Caucasians and these Asian groups (all P < 0.0001).
  
  
  CONCLUSIONS
  Our study suggests a higher chance to detect the association between rs947211 and PD in Chinese, Malay, and other Caucasian groups because of the similar linkage disequilibrium pattern around rs947211. The associations between rs823128/rs823156/rs708730 and PD are more likely to be replicated in Chinese and Malay populations.
authors.affiliation: Health Services Research and Biostatistics Unit, Division of Research, Singapore General Hospital.
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Statistics & Applied Probability, Saw Swee Hock School of Public Health, National University of Singapore.
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.affiliation: Departments of Clinical Research and Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, Duke NUS Graduate Medical School.
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics*; D008296:Malaysia; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012846:Singapore; D044465:White People / Q000235:genetics*
keywords: PARK16 gene; Parkinson's disease; genomewide association studies; linkage disequilibrium; varLD score