The fine-scale genetic structure and evolution of the Japanese population

Takeuchi, Fumihiko; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Isomura, Minoru; Ohkubo, Takayoshi; Tabara, Yasuharu; Yamamoto, Ken; Yokota, Mitsuhiro; Liu, Xuanyao; Saw, Woei-Yuh; Mamatyusupu, Dolikun; Yang, Wenjun; Xu, Shuhua; Teo, Yik-Ying; Kato, Norihiro

doi:10.1371/journal.pone.0185487

Cited by 29 publications

(31 citation statements)

References 59 publications

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“…The distribution of the individuals projected onto the two-dimensional space by PCA largely reflected the geographic distribution. The PC1 corresponded to the northeast-tosouthwest geographic axis, which separated the Japanese population into two major clusters, as reported previously 16,20 . The "Hondo" cluster consisted mainly of the residents of the mainland (the four major Japanese islands, which included six regions in this study [i.e., Hokkaido, Tohoku, Kanto-Koshinetsu, Chubu-Hokuriku, Kinki, and Kyushu]; Supplementary Fig.…”

Section: Resultssupporting

confidence: 80%

“…Japan, located far east of Africa and Europe as one of the ends of the human journey, has experienced a unique demographic history. One hypothesis assumes that two waves of human migration into Japan occurred: one from Southeast Asia 40,000 years ago, followed by another from the Korean Peninsula 3000 years ago 15,16 . Few admixture events have taken place after these migratory waves, and the population has been kept isolated within the mainland and the surrounding thousands of small islands.…”

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confidence: 99%

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Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences for polygenic risk prediction

et al. 2020

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The diversity in our genome is crucial to understanding the demographic history of worldwide populations. However, we have yet to know whether subtle genetic differences within a population can be disentangled, or whether they have an impact on complex traits. Here we apply dimensionality reduction methods (PCA, t-SNE, PCA-t-SNE, UMAP, and PCA-UMAP) to biobank-derived genomic data of a Japanese population (n = 169,719). Dimensionality reduction reveals fine-scale population structure, conspicuously differentiating adjacent insular subpopulations. We further enluciate the demographic landscape of these Japanese subpopulations using population genetics analyses. Finally, we perform phenome-wide polygenic risk score (PRS) analyses on 67 complex traits. Differences in PRS between the deconvoluted subpopulations are not always concordant with those in the observed phenotypes, suggesting that the PRS differences might reflect biases from the uncorrected structure, in a trait-dependent manner. This study suggests that such an uncorrected structure can be a potential pitfall in the clinical application of PRS.

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Section: Resultssupporting

confidence: 80%

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confidence: 99%

Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences for polygenic risk prediction

et al. 2020

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“…It appears that within-country population structure occurs across the world 6,25 , and in this study is observed down to scales of less than 10km. Such strong, localised genetic drift predicts the existence of geographically localised rare mutations, including pathogenic ones.…”

Section: Discussionmentioning

confidence: 51%

Patterns of genetic differentiation and the footprints of historical migrations in the Iberian Peninsula

Bycroft

Fernández–Rozadilla

Ruíz-Ponte

et al. 2018

Preprint

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Genetic differences within or between human populations (population structure) has been studied using a variety of approaches over many years. Recently there has been an increasing focus on studying genetic differentiation at fine geographic scales, such as within countries. Identifying such structure allows the study of recent population history, and identifies the potential for confounding in association studies, particularly when testing rare, often recently arisen variants. The Iberian Peninsula is linguistically diverse, has a complex demographic history, and is unique among European regions in having a centuries-long period of Muslim rule. Previous genetic studies of Spain have examined either a small fraction of the genome or only a few Spanish regions. Thus, the overall pattern of fine-scale population structure within Spain remains uncharacterised. Here we analyse genome-wide genotyping array data for 1,413 Spanish individuals sampled from all regions of Spain. We identify extensive fine-scale structure, down to unprecedented scales, smaller than 10 Km in some places. We observe a major axis of genetic differentiation that runs from east to west of the peninsula. In contrast, we observe remarkable genetic similarity in the north-south direction, and evidence of historical north-south population movement. Finally, without making particular prior assumptions about source populations, we show that modern Spanish people have regionally varying fractions of ancestry from a group most similar to modern north Moroccans. The north African ancestry results from an admixture event, which we date to 860 - 1120 CE, corresponding to the early half of Muslim rule. Our results indicate that it is possible to discern clear genetic impacts of the Muslim conquest and population movements associated with the subsequent Reconquista.

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“…Recent studies have showcased the power of leveraging shared haplotypes to uncover and characterise previously unrecognised fine-grained genetic structure within populations, yielding novel insights into the demographic composition and history of Britain and Ireland 4–7 , Finland 8 , Japan 9 , Italy 10 and Spain 11 . Haplotype sharing has also revealed genetic affinities between populations, enabling inference of historical admixture events using modern populations as proxies for ancestral admixing sources 12 .…”

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confidence: 99%

Dutch population structure across space, time and GWAS design

Byrne

Rheenen

Berg

et al. 2020

Preprint

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We studied fine-grained population genetic structure and demographic change across the Netherlands using 1 genome-wide single nucleotide polymorphism data (1,626 individuals) with associated geography (1,422 2 individuals). We applied ChromoPainter/fineSTRUCTURE, identifying 40 haplotypic clusters exhibiting 3 strong north/south variation and fine-scale differentiation within provinces. Clustering is tied to country-wide 4 ancestry gradients from neighbouring lands and to locally restricted gene flow across major Dutch rivers. 5 Despite superexponential population growth, north-south structure is temporally stable, with west-east 6 differentiation more transient, potentially influenced by migrations during the middle ages. Within Dutch 7 and international data, GWAS incorporating fine-grained haplotypic covariates are less confounded than 8 standard methods. 9 The Netherlands is a densely populated country on the northwestern edge of the European continent, bounded by 10 Germany, Belgium and the North Sea. The country is divided into twelve provinces and has a complex demographic 11 history, with occupation by several Germanic peoples since the collapse of the Roman Empire, including the 12 Frisians, the Low Saxons and the Franks. Over 17 million individuals now inhabit this relatively small region 13 (41,500km 2 ), making it one of the most densely populated countries in Europe. Despite its small geographical size, 14 previous genetic studies of the people of the Netherlands have demonstrated coarse population structure that 15 correlates with its geography, as well as apparent heterogeneity in effective population sizes across provinces 1,2 . 16 These observations suggest that the demographic past of the Dutch population has left residual signatures in its 17 present regional genetic structure; however this has not been fully explained in the context of neighbouring 18 populations and thus far the use of unlinked genetic markers have limited the resolution at which this structure can 19 be described. This resolution limit also confines the extent to which the confounding effects of population structure 20 can be controlled in genomic studies of health and disease such as genome-wide association studies (GWAS). As 21 these studies continue to seek ever-rarer genetic variation with ever-increasing cohort sizes, intricate understanding 22 and fine control of population structure is becoming increasingly relevant, but increasingly challenging 3 . 23 Recent studies have showcased the power of leveraging shared haplotypes to uncover and characterise previously 24 unrecognised fine-grained genetic structure within populations, yielding novel insights into the demographic 25 composition and history of Britain and Ireland 4-7 , Finland 8 , Japan 9 , Italy 10 and Spain 11 . Haplotype sharing has also 26 revealed genetic affinities between populations, enabling inference of historical admixture events using modern 27 populations as proxies for ancestral admixing sources 12 . Furthermore, geographic informat...

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The fine-scale genetic structure and evolution of the Japanese population

Cited by 29 publications

References 59 publications

Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences for polygenic risk prediction

Dimensionality reduction reveals fine-scale structure in the Japanese population with consequences for polygenic risk prediction

Patterns of genetic differentiation and the footprints of historical migrations in the Iberian Peninsula

Dutch population structure across space, time and GWAS design

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