Genome-wide methylation data mirror ancestry information.
Genetic data are known to harbor information about human demographics, and genotyping data are commonly used for capturing ancestry information by leveraging genome-wide differences between populations. In contrast, it is not clear to what extent population structure is captured by whole-genome DNA methylation data.



We demonstrate, using three large-cohort 450K methylation array data sets, that ancestry information signal is mirrored in genome-wide DNA methylation data and that it can be further isolated more effectively by leveraging the correlation structure of CpGs withcis-located SNPs. Based on these insights, we propose a method, EPISTRUCTURE, for the inference of ancestry from methylation data, without the need for genotype data.



EPISTRUCTURE can be used to infer ancestry information of individuals based on their methylation data in the absence of corresponding genetic data. Although genetic data are often collected in epigenetic studies of large cohorts, these are typically not made publicly available, making the application of EPISTRUCTURE especially useful for anyone working on public data. Implementation of EPISTRUCTURE is available in GLINT, our recently released toolset for DNA methylation analysis at: http://glint-epigenetics.readthedocs.io.
Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
Elior
0000-0002-9017-2070
E
Rahmani
Department of Statistics, Tel Aviv University, Tel Aviv, Israel.
Liat
L
Shenhav
Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
Regev
R
Schweiger
Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California Berkeley, Berkeley, CA USA.
Paul
P
Yousefi
Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California Berkeley, Berkeley, CA USA.
Karen
K
Huen
Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California Berkeley, Berkeley, CA USA.
Brenda
B
Eskenazi
Department of Medicine, University of California San Francisco, San Francisco, CA USA.
Celeste
C
Eng
Department of Medicine, University of California San Francisco, San Francisco, CA USA.
Scott
S
Huntsman
Department of Medicine, University of California San Francisco, San Francisco, CA USA.
Donglei
D
Hu
Department of Medicine, University of California San Francisco, San Francisco, CA USA.|Department of Bioengineering and Therapeutic Science, University of California San Francisco, San Francisco, CA USA.
Joshua
J
Galanter
Department of Medicine, University of California San Francisco, San Francisco, CA USA.
Sam S
SS
Oh
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Melanie
M
Waldenberger
Institute of Genetic Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.|Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
Konstantin
K
Strauch
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
Harald
H
Grallert
Institute of Human Genetics, Helmholtz Zentrum München, Munich, Germany.|Institute of Human Genetics, Technische Universität München, Munich, Germany.
Thomas
T
Meitinger
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
Christian
C
Gieger
Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California Berkeley, Berkeley, CA USA.
Nina
N
Holland
Department of Medicine, University of California San Francisco, San Francisco, CA USA.|Department of Bioengineering and Therapeutic Science, University of California San Francisco, San Francisco, CA USA.
Esteban G
EG
Burchard
Department of Medicine, University of California San Francisco, San Francisco, CA USA.
Noah
N
Zaitlen
Department of Computer Science, University of California Los Angeles, Los Angeles, CA USA.|Department of Anesthesiology and Perioperative Medicine, University of California Los Angeles, Los Angeles, CA USA.
Eran
E
Halperin
D000465:Algorithms; D018899:CpG Islands; D019175:DNA Methylation; D030541:Databases, Genetic; D057890:Epigenomics / Q000379:methods*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020407:Internet; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D014584:User-Computer Interface
Ancestry; DNA methylation; Epigenetics; Epigenome-wide association study (EWAS); Illumina 450K; Population structure