Byrne Ross P, van Rheenen Wouter, van den Berg Leonard H, Veldink Jan H, McLaughlin Russell L
Smurfit Institute of Genetics, Trinity College Dublin, Dublin, D02 DK07, Republic of Ireland.
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
Nat Commun. 2020 Sep 11;11(1):4556. doi: 10.1038/s41467-020-18418-4.
Previous genetic studies have identified local population structure within the Netherlands; however their resolution is limited by use of unlinked markers and absence of external reference data. Here we apply advanced haplotype sharing methods (ChromoPainter/fineSTRUCTURE) to study fine-grained population genetic structure and demographic change across the Netherlands using genome-wide single nucleotide polymorphism data (1,626 individuals) with associated geography (1,422 individuals). We identify 40 haplotypic clusters exhibiting strong north/south variation and fine-scale differentiation within provinces. Clustering is tied to country-wide ancestry gradients from neighbouring lands and to locally restricted gene flow across major Dutch rivers. North-south structure is temporally stable, with west-east differentiation more transient, potentially influenced by migrations during the middle ages. Despite superexponential population growth, regional demographic estimates reveal population crashes contemporaneous with the Black Death. Within Dutch and international data, GWAS incorporating fine-grained haplotypic covariates are less confounded than standard methods.
先前的基因研究已经确定了荷兰境内的本地种群结构；然而，它们的分辨率受到未连锁标记的使用以及缺乏外部参考数据的限制。在这里，我们应用先进的单倍型共享方法（ChromoPainter/fineSTRUCTURE），使用全基因组单核苷酸多态性数据（1626名个体）及相关地理信息（1422名个体），来研究荷兰境内细粒度的种群遗传结构和人口变化。我们识别出40个单倍型簇，这些簇在省内呈现出强烈的南北差异和精细尺度的分化。聚类与来自邻国的全国祖先梯度以及荷兰主要河流上局部受限的基因流动有关。南北结构在时间上是稳定的，而东西分化则更具瞬变性，这可能受到中世纪移民的影响。尽管人口呈超指数增长，但区域人口估计显示，人口崩溃与黑死病同时发生。在荷兰和国际数据中，纳入细粒度单倍型协变量的全基因组关联研究（GWAS）比标准方法的混淆性更小。
