Whole-genome sequence variation, population structure and demographic history of the Dutch population

The Genome of the Netherlands consortium; A.J. de Craen; H.E.D. Suchiman; A. Hofman; B.A. Oostra; A.G. Uitterlinden; G. Willemsen; M. Platteel; J.H. Veldink; L.H. Van den Berg; S.J. Pitts; S. Potluri; P. Sundar; D.R. Cox; S.R. Sunyaev; J.T. den Dunnen; M. Stoneking; P. de Knijff; M. Kayser; Q. Li; Y. Li; Y. Du; R. Chen; H. Cao; S. Cao; J. Wang; J.A. Bovenberg; I. Pe'er; P.E. Slagboom; C.M. van Duijn; D.I. Boomsma; G.J.B van Ommen; P.I.W. Bakker; M. Swertz; C. Wijmenga

doi:https://doi.org/10.1038/ng.3021

Whole-genome sequence variation, population structure and demographic history of the Dutch population

The Genome of the Netherlands consortium, A.J. de Craen, H.E.D. Suchiman, A. Hofman, B.A. Oostra, A.G. Uitterlinden, G. Willemsen, M. Platteel, J.H. Veldink, L.H. Van den Berg, S.J. Pitts, S. Potluri, P. Sundar, D.R. Cox, S.R. Sunyaev, J.T. den Dunnen, M. Stoneking, P. de Knijff, M. Kayser, Q. LiY. Li, Y. Du, R. Chen, H. Cao, S. Cao, J. Wang, J.A. Bovenberg, I. Pe'er, P.E. Slagboom, C.M. van Duijn, D.I. Boomsma, G.J.B van Ommen, P.I.W. Bakker, M. Swertz, C. Wijmenga

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Abstract

Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.

Original language	English
Pages (from-to)	818-825
Number of pages	8
Journal	Nature Genetics
Volume	46
Issue number	8
DOIs	https://doi.org/10.1038/ng.3021
Publication status	Published - Aug 2014

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The Genome of the Netherlands consortium, de Craen, A. J., Suchiman, H. E. D., Hofman, A., Oostra, B. A., Uitterlinden, A. G., Willemsen, G., Platteel, M., Veldink, J. H., Van den Berg, L. H., Pitts, S. J., Potluri, S., Sundar, P., Cox, D. R., Sunyaev, S. R., den Dunnen, J. T., Stoneking, M., de Knijff, P., Kayser, M., ... Wijmenga, C. (2014). Whole-genome sequence variation, population structure and demographic history of the Dutch population. Nature Genetics, 46(8), 818-825. https://doi.org/10.1038/ng.3021

@article{0ddc3789a07840d3a059f1cecf9a95cb,

title = "Whole-genome sequence variation, population structure and demographic history of the Dutch population",

abstract = "Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.",

author = "{The Genome of the Netherlands consortium} and Francioli, {Laurent C.} and Androniki Menelaou and Pulit, {Sara L.} and {Van Dijk}, Freerk and Palamara, {Pier Francesco} and Elbers, {Clara C.} and Neerincx, {Pieter B.T.} and Kai Ye and Victor Guryev and Kloosterman, {Wigard P.} and Patrick Deelen and Abdel Abdellaoui and {Van Leeuwen}, {Elisabeth M.} and {Van Oven}, Mannis and Martijn Vermaat and Mingkun Li and Laros, {Jeroen F.J.} and Karssen, {Lennart C.} and Alexandros Kanterakis and Najaf Amin and Hottenga, {Jouke Jan} and Lameijer, {Eric Wubbo} and Mathijs Kattenberg and Martijn Dijkstra and Heorhiy Byelas and {Van Setten}, Jessica and {Van Schaik}, {Barbera D.C.} and Jan Bot and Nijman, {Isa{\"a}c J.} and Ivo Renkens and Tobias Marschall and Alexander Sch{\"o}nhuth and Hehir-Kwa, {Jayne Y.} and Handsaker, {Robert E.} and Paz Polak and Mashaal Sohail and Dana Vuzman and Fereydoun Hormozdiari and {Van Enckevort}, David and Hailiang Mei and Vyacheslav Koval and Moed, {Matthijs H.} and {Van Der Velde}, KJoeri and Fernando Rivadeneira and Karol Estrada and Carolina Medina-Gomez and Aaron Isaacs and McCarroll, {Steven A.} and Marian Beekman and {Mde Craen}, {Anton J.} and {de Craen}, A.J. and H.E.D. Suchiman and A. Hofman and B.A. Oostra and A.G. Uitterlinden and G. Willemsen and M. Platteel and J.H. Veldink and {Van den Berg}, L.H. and S.J. Pitts and S. Potluri and P. Sundar and D.R. Cox and S.R. Sunyaev and {den Dunnen}, J.T. and M. Stoneking and {de Knijff}, P. and M. Kayser and Q. Li and Y. Li and Y. Du and R. Chen and H. Cao and S. Cao and J. Wang and J.A. Bovenberg and I. Pe'er and P.E. Slagboom and {van Duijn}, C.M. and D.I. Boomsma and {van Ommen}, G.J.B and P.I.W. Bakker and M. Swertz and C. Wijmenga",

note = "Funding Information: We wish to dedicate this work to the memory of David R. Cox, an enthusiastic supporter of human genetic research in the Netherlands for many years. The GoNL Project is funded by the BBMRI-NL, a research infrastructure financed by the Netherlands Organization for Scientific Research (NWO project 184.021.007). We acknowledge additional financial support from eBioGrid, CTMM/TraIT, the Ubbo Emmius Fund, the Netherlands Bioinformatics Center (NBIC) and EU-BioSHARE. We thank the individual participants of the biobanks; M. Depristo, E. Banks, R. Poplin and G. del Angel from the Broad Institute for expert advice on setting up our alignment and calling pipeline; K. Garimella for the initial implementation of PhaseByTransmission; G. Strikwerda, W. Albers, R. Teeninga, H. Gankema and H. Wind of the Groningen Center for Information Technology (see URLs) for support of the compute cluster and Target storage; E. Valentyn and R. Williams of Target (see URLs) for hosting project data on IBM GPFS storage; T. Visser and I. Nooren of BiG Grid (see URLs) and SURFsara for providing backup storage, additional computing capacity and expert advice; the team from MOLGENIS (see URLs) for software development support; H. Lauvenberg for handling data access requests; K. Zych for design of the GoNL logo; L. Franke, H.-J. Westra and J. Gutierrez-Achury for useful discussions; and S. Raychaudhuri and B. Neale for their critical reading of the manuscript. Target is supported by Samenwerkingsverband Noord Nederland, the European Fund for Regional Development, the Dutch Ministry of Economic Affairs, Pieken in de Delta and the provinces of Groningen and Drenthe. Target operates under the auspices of Sensor Universe. BiG Grid and the Life Science Grid are financially supported by the Netherlands Organization for Scientific Research (NWO). A.A. is funded by the Center for Medical Systems Biology-2, and D.I.B. is funded by the European Research Council (ERC 230374). A.S. and P.I.W.d.B. are recipients of VIDI awards (NWO projects 016.138.318 and 016.126.354, respectively).",

year = "2014",

month = aug,

doi = "https://doi.org/10.1038/ng.3021",

language = "English",

volume = "46",

pages = "818--825",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "8",

}

The Genome of the Netherlands consortium, de Craen, AJ, Suchiman, HED, Hofman, A, Oostra, BA, Uitterlinden, AG, Willemsen, G, Platteel, M, Veldink, JH, Van den Berg, LH, Pitts, SJ, Potluri, S, Sundar, P, Cox, DR, Sunyaev, SR, den Dunnen, JT, Stoneking, M, de Knijff, P, Kayser, M, Li, Q, Li, Y, Du, Y, Chen, R, Cao, H, Cao, S, Wang, J, Bovenberg, JA, Pe'er, I, Slagboom, PE, van Duijn, CM, Boomsma, DI, van Ommen, GJB, Bakker, PIW, Swertz, M & Wijmenga, C 2014, 'Whole-genome sequence variation, population structure and demographic history of the Dutch population', Nature Genetics, vol. 46, no. 8, pp. 818-825. https://doi.org/10.1038/ng.3021

TY - JOUR

T1 - Whole-genome sequence variation, population structure and demographic history of the Dutch population

AU - The Genome of the Netherlands consortium

AU - Francioli, Laurent C.

AU - Menelaou, Androniki

AU - Pulit, Sara L.

AU - Van Dijk, Freerk

AU - Palamara, Pier Francesco

AU - Elbers, Clara C.

AU - Neerincx, Pieter B.T.

AU - Ye, Kai

AU - Guryev, Victor

AU - Kloosterman, Wigard P.

AU - Deelen, Patrick

AU - Abdellaoui, Abdel

AU - Van Leeuwen, Elisabeth M.

AU - Van Oven, Mannis

AU - Vermaat, Martijn

AU - Li, Mingkun

AU - Laros, Jeroen F.J.

AU - Karssen, Lennart C.

AU - Kanterakis, Alexandros

AU - Amin, Najaf

AU - Hottenga, Jouke Jan

AU - Lameijer, Eric Wubbo

AU - Kattenberg, Mathijs

AU - Dijkstra, Martijn

AU - Byelas, Heorhiy

AU - Van Setten, Jessica

AU - Van Schaik, Barbera D.C.

AU - Bot, Jan

AU - Nijman, Isaäc J.

AU - Renkens, Ivo

AU - Marschall, Tobias

AU - Schönhuth, Alexander

AU - Hehir-Kwa, Jayne Y.

AU - Handsaker, Robert E.

AU - Polak, Paz

AU - Sohail, Mashaal

AU - Vuzman, Dana

AU - Hormozdiari, Fereydoun

AU - Van Enckevort, David

AU - Mei, Hailiang

AU - Koval, Vyacheslav

AU - Moed, Matthijs H.

AU - Van Der Velde, KJoeri

AU - Rivadeneira, Fernando

AU - Estrada, Karol

AU - Medina-Gomez, Carolina

AU - Isaacs, Aaron

AU - McCarroll, Steven A.

AU - Beekman, Marian

AU - Mde Craen, Anton J.

AU - de Craen, A.J.

AU - Suchiman, H.E.D.

AU - Hofman, A.

AU - Oostra, B.A.

AU - Uitterlinden, A.G.

AU - Willemsen, G.

AU - Platteel, M.

AU - Veldink, J.H.

AU - Van den Berg, L.H.

AU - Pitts, S.J.

AU - Potluri, S.

AU - Sundar, P.

AU - Cox, D.R.

AU - Sunyaev, S.R.

AU - den Dunnen, J.T.

AU - Stoneking, M.

AU - de Knijff, P.

AU - Kayser, M.

AU - Li, Q.

AU - Li, Y.

AU - Du, Y.

AU - Chen, R.

AU - Cao, H.

AU - Cao, S.

AU - Wang, J.

AU - Bovenberg, J.A.

AU - Pe'er, I.

AU - Slagboom, P.E.

AU - van Duijn, C.M.

AU - Boomsma, D.I.

AU - van Ommen, G.J.B

AU - Bakker, P.I.W.

AU - Swertz, M.

AU - Wijmenga, C.

N1 - Funding Information: We wish to dedicate this work to the memory of David R. Cox, an enthusiastic supporter of human genetic research in the Netherlands for many years. The GoNL Project is funded by the BBMRI-NL, a research infrastructure financed by the Netherlands Organization for Scientific Research (NWO project 184.021.007). We acknowledge additional financial support from eBioGrid, CTMM/TraIT, the Ubbo Emmius Fund, the Netherlands Bioinformatics Center (NBIC) and EU-BioSHARE. We thank the individual participants of the biobanks; M. Depristo, E. Banks, R. Poplin and G. del Angel from the Broad Institute for expert advice on setting up our alignment and calling pipeline; K. Garimella for the initial implementation of PhaseByTransmission; G. Strikwerda, W. Albers, R. Teeninga, H. Gankema and H. Wind of the Groningen Center for Information Technology (see URLs) for support of the compute cluster and Target storage; E. Valentyn and R. Williams of Target (see URLs) for hosting project data on IBM GPFS storage; T. Visser and I. Nooren of BiG Grid (see URLs) and SURFsara for providing backup storage, additional computing capacity and expert advice; the team from MOLGENIS (see URLs) for software development support; H. Lauvenberg for handling data access requests; K. Zych for design of the GoNL logo; L. Franke, H.-J. Westra and J. Gutierrez-Achury for useful discussions; and S. Raychaudhuri and B. Neale for their critical reading of the manuscript. Target is supported by Samenwerkingsverband Noord Nederland, the European Fund for Regional Development, the Dutch Ministry of Economic Affairs, Pieken in de Delta and the provinces of Groningen and Drenthe. Target operates under the auspices of Sensor Universe. BiG Grid and the Life Science Grid are financially supported by the Netherlands Organization for Scientific Research (NWO). A.A. is funded by the Center for Medical Systems Biology-2, and D.I.B. is funded by the European Research Council (ERC 230374). A.S. and P.I.W.d.B. are recipients of VIDI awards (NWO projects 016.138.318 and 016.126.354, respectively).

PY - 2014/8

Y1 - 2014/8

N2 - Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.

AB - Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (∼13×) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies.

UR - http://www.scopus.com/inward/record.url?scp=84905579746&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/ng.3021

DO - https://doi.org/10.1038/ng.3021

M3 - Article

C2 - 24974849

SN - 1061-4036

VL - 46

SP - 818

EP - 825

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Whole-genome sequence variation, population structure and demographic history of the Dutch population

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Cohort Studies

UN SDGs

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