Using ancestry-informative markers to identify fine structure across 15 populations of European origin

Laura M. Huckins; Vesna Boraska; Christopher S. Franklin; James A.B. Floyd; Lorraine Southam; GCAN; WTCCC3; Patrick F. Sullivan; Cynthia M. Bulik; David A. Collier; Chris Tyler-Smith; Eleftheria Zeggini; Ioanna Tachmazidou

doi:10.1038/ejhg.2014.1

Using ancestry-informative markers to identify fine structure across 15 populations of European origin

Laura M. Huckins^* (Corresponding Author), Vesna Boraska, Christopher S. Franklin, James A.B. Floyd, Lorraine Southam, GCAN, WTCCC3, Patrick F. Sullivan, Cynthia M. Bulik, David A. Collier, Chris Tyler-Smith, Eleftheria Zeggini, Ioanna Tachmazidou

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia.

Original language	English
Pages (from-to)	1190-1200
Number of pages	11
Journal	European Journal of Human Genetics
Volume	22
Issue number	10
DOIs	https://doi.org/10.1038/ejhg.2014.1
Publication status	Published - 11 Oct 2014

Bibliographical note

Funding Information:
LMH, VB, CSF, JABF, LS, CTS, IT and EZ were supported by the Wellcome Trust (098051). LMH is also supported by the MRC (MR/J500355/1), VB is also supported by Unity Through Knowledge Fund CONNECTIVITY PROGRAM (‘Gaining Experience’ Grant 2A), The National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia (BRAIN GAIN-Postdoc fellowship) and CMB is supported by the Foundation of Hope.

Publisher Copyright:
© 2014 Macmillan Publishers Limited All rights reserved.

Keywords

AIMs
population stratification
principal component analysis

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10.1038/ejhg.2014.1

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Huckins, L. M., Boraska, V., Franklin, C. S., Floyd, J. A. B., Southam, L., GCAN, WTCCC3, Sullivan, P. F., Bulik, C. M., Collier, D. A., Tyler-Smith, C., Zeggini, E., & Tachmazidou, I. (2014). Using ancestry-informative markers to identify fine structure across 15 populations of European origin. European Journal of Human Genetics, 22(10), 1190-1200. https://doi.org/10.1038/ejhg.2014.1

Huckins, LM, Boraska, V, Franklin, CS, Floyd, JAB, Southam, L, GCAN, WTCCC3, Sullivan, PF, Bulik, CM, Collier, DA, Tyler-Smith, C, Zeggini, E & Tachmazidou, I 2014, 'Using ancestry-informative markers to identify fine structure across 15 populations of European origin', European Journal of Human Genetics, vol. 22, no. 10, pp. 1190-1200. https://doi.org/10.1038/ejhg.2014.1

@article{0087c123186242eaaf8fdda4224864e4,

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abstract = "The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia.",

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author = "Huckins, {Laura M.} and Vesna Boraska and Franklin, {Christopher S.} and Floyd, {James A.B.} and Lorraine Southam and GCAN and WTCCC3 and Sullivan, {Patrick F.} and Bulik, {Cynthia M.} and Collier, {David A.} and Chris Tyler-Smith and Eleftheria Zeggini and Ioanna Tachmazidou and Thornton, {L. M.} and {William Rayner}, N. and Klump, {K. L.} and J. Treasure and U. Schmidt and F. Tozzi and K. Kiezebrink and J. Hebebrand and P. Gorwood and Adan, {R. A.H.} and Kas, {M. J.H.} and A. Favaro and P. Santonastaso and F. Fern{\'a}ndez-Aranda and M. Gratacos and F. Rybakowski and M. Dmitrzak-Weglarz and J. Kaprio and A. Keski-Rahkonen and A. Raevuori and {Van Furth}, {E. F.} and {Slof-Op t Landt}, {M. C.T.} and Hudson, {J. I.} and T. Reichborn-Kjennerud and Knudsen, {G. P.S.} and P. Monteleone and Kaplan, {A. S.} and A. Karwautz and H. Hakonarson and Berrettini, {W. H.} and Y. Guo and D. Li and Schork, {N. J.} and G. Komaki and T. Ando and H. Inoko and T. Esko and K. Fischer and K. M{\"a}nnik",

note = "Funding Information: LMH, VB, CSF, JABF, LS, CTS, IT and EZ were supported by the Wellcome Trust (098051). LMH is also supported by the MRC (MR/J500355/1), VB is also supported by Unity Through Knowledge Fund CONNECTIVITY PROGRAM ({\textquoteleft}Gaining Experience{\textquoteright} Grant 2A), The National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia (BRAIN GAIN-Postdoc fellowship) and CMB is supported by the Foundation of Hope. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited All rights reserved.",

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AU - Huckins, Laura M.

AU - Boraska, Vesna

AU - Franklin, Christopher S.

AU - Floyd, James A.B.

AU - Southam, Lorraine

AU - GCAN

AU - WTCCC3

AU - Sullivan, Patrick F.

AU - Bulik, Cynthia M.

AU - Collier, David A.

AU - Tyler-Smith, Chris

AU - Zeggini, Eleftheria

AU - Tachmazidou, Ioanna

AU - Thornton, L. M.

AU - William Rayner, N.

AU - Klump, K. L.

AU - Treasure, J.

AU - Schmidt, U.

AU - Tozzi, F.

AU - Kiezebrink, K.

AU - Hebebrand, J.

AU - Gorwood, P.

AU - Adan, R. A.H.

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AU - Santonastaso, P.

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AU - Gratacos, M.

AU - Rybakowski, F.

AU - Dmitrzak-Weglarz, M.

AU - Kaprio, J.

AU - Keski-Rahkonen, A.

AU - Raevuori, A.

AU - Van Furth, E. F.

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AU - Reichborn-Kjennerud, T.

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AU - Monteleone, P.

AU - Kaplan, A. S.

AU - Karwautz, A.

AU - Hakonarson, H.

AU - Berrettini, W. H.

AU - Guo, Y.

AU - Li, D.

AU - Schork, N. J.

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AU - Ando, T.

AU - Inoko, H.

AU - Esko, T.

AU - Fischer, K.

AU - Männik, K.

N1 - Funding Information: LMH, VB, CSF, JABF, LS, CTS, IT and EZ were supported by the Wellcome Trust (098051). LMH is also supported by the MRC (MR/J500355/1), VB is also supported by Unity Through Knowledge Fund CONNECTIVITY PROGRAM (‘Gaining Experience’ Grant 2A), The National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia (BRAIN GAIN-Postdoc fellowship) and CMB is supported by the Foundation of Hope. Publisher Copyright: © 2014 Macmillan Publishers Limited All rights reserved.

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N2 - The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia.

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Using ancestry-informative markers to identify fine structure across 15 populations of European origin

Abstract

Bibliographical note

Keywords

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