Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A
Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A
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DOI：
10.1186/s12881-016-0341-z
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发表时间：
2016-11-15
影响因子：
--
通讯作者：
Wilcox, Phillip L.
中科院分区：
文献类型：
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作者：
Cadzow, Murray;Merriman, Tony R.;Wilcox, Phillip L.
背景资料：PPARGC 1A基因，特别是Gly 482 Ser变体（rs 8192678），被认为是自然选择的产物，特别是在现存波利尼西亚人的祖先中。原因包括高水平的人口分化和衍生的2型糖尿病（T2 D）风险482 Ser等位基因的频率增加，以及与汤加小人口中的体重指数（BMI）的相关性。然而，没有直接的统计检验的选择已applied.Methods：使用一系列的波利尼西亚人群（汤加，毛利，萨摩亚），我们重新研究的证据之间的关联Gly 482 Ser与T2 D和BMI以及痛风。还使用亚洲，欧洲和非洲1000个基因组计划样本进行了一系列统计测试，对PPARGC 1A基因座进行FST、整合单倍型评分（iHS）、交叉群体扩展单倍型纯合性（XP-EHH）、Tajima's D和Fay and Wu's H。Gly 482 Ser与任何BMI之间无统计学显著相关性证据，T2 D或痛风。亚洲和太平洋地区人群（新西兰毛利人）之间的人群分化（F-ST）最小
Background: The gene PPARGC1A, in particular the Gly482Ser variant (rs8192678), had been proposed to be subject to natural selection, particularly in recent progenitors of extant Polynesian populations. Reasons include high levels of population differentiation and increased frequencies of the derived type 2 diabetes (T2D) risk 482Ser allele, and association with body mass index (BMI) in a small Tongan population. However, no direct statistical tests for selection have been applied.Methods: Using a range of Polynesian populations (Tongan, Maori, Samoan) we re-examined evidence for association between Gly482Ser with T2D and BMI as well as gout. Using also Asian, European, and African 1000 Genome Project samples a range of statistical tests for selection (FST, integrated haplotype score (iHS), cross population extended haplotype homozygosity (XP-EHH), Tajima's D and Fay and Wu's H) were conducted on the PPARGC1A locus.Results: No statistically significant evidence for association between Gly482Ser and any of BMI, T2D or gout was found. Population differentiation (F-ST) was smallest between Asian and Pacific populations (New Zealand Maori