Health Services Research and Biostatistics Unit, Division of Research, Singapore General Hospital.
Department of Statistics & Applied Probability, Saw Swee Hock School of Public Health, National University of Singapore.
Mov Disord. 2015 Sep;30(10):1335-42. doi: 10.1002/mds.26176. Epub 2015 Mar 11.
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).
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.
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).
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.
在不同人群中重现全基因组关联研究结果具有挑战性，因为可重复性从根本上依赖于未知因果变异与已分型的单核苷酸多态性（SNP）之间的连锁不平衡模式相似。
PARK16 基因座在全基因组关联研究中被报道改变了日本人与高加索人群患帕金森病（PD）的风险。我们通过 Monte Carlo 模拟，使用传统的热图和对 PARK16 基因的靶向分析，评估了来自 HapMap 的高加索人、日本人以及中国人，和来自新加坡基因组变异计划的中国人、马来人和印度人在 PARK16 基因座的区域连锁不平衡模式，并通过这些族群的 varLD 分数进行评估。
纳入了来自 HapMap 的 100 个高加索人 SNP、95 个中国人 SNP、78 个日本人 SNP、86 个中国人 SNP、99 个印度人 SNP 和 97 个马来西亚人 SNP。我们的靶向分析显示，rs947211 附近 SNP 的连锁不平衡模式在高加索人与亚洲人（包括中国人、日本人、和马来人）中相似（均 P > 0.0001），而在 rs823128、rs823156 和 rs708730 周围的连锁不平衡模式在高加索人与这些亚洲人群之间存在差异（均 P < 0.0001）。
我们的研究表明，由于 rs947211 周围的连锁不平衡模式相似，中国人、马来人和其他高加索人群检测 rs947211 与 PD 之间的关联的可能性更高。rs823128/rs823156/rs708730 与 PD 之间的关联更有可能在中国人和马来人群中得到复制。
