Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

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Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits. / Tachmazidou, Ioanna; Süveges, Dániel; Min, Josine L; Ritchie, Graham R S; Steinberg, Julia; Walter, Klaudia; Iotchkova, Valentina; Schwartzentruber, Jeremy; Huang, Jie; Memari, Yasin; McCarthy, Shane; Crawford, Andrew J.; Bombieri, Cristina; Cocca, Massimiliano; Farmaki, Aliki-Eleni; Gaunt, Tom R; Jousilahti, Pekka; Kooijman, Marjolein N; Lehne, Benjamin; Malerba, Giovanni; Männistö, Satu; Matchan, Angela; Medina-Gomez, Carolina; Metrustry, Sarah J; Nag, Abhishek; Ntalla, Ioanna; Paternoster, Lavinia; Rayner, Nigel W; Sala, Cinzia; Scott, William R; Shihab, Hashem A.; Southam, Lorraine; St Pourcain, Beate; Traglia, Michela; Trajanoska, Katerina; Zaza, Gialuigi; Zhang, Weihua; Artigas, Maria Soler; Bansal, Narinder; Benn, Marianne; Chen, Zhongsheng; Danecek, Petr; Lin, Wei-Yu; Locke, Adam E; Luan, Jian'an; Manning, Alisa K; Mulas, Antonella; Sidore, Carlo; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G; SpiroMeta Consortium.

I: American Journal of Human Genetics, Bind 100, Nr. 6, 01.06.2017, s. 865-884.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Tachmazidou, I, Süveges, D, Min, JL, Ritchie, GRS, Steinberg, J, Walter, K, Iotchkova, V, Schwartzentruber, J, Huang, J, Memari, Y, McCarthy, S, Crawford, AJ, Bombieri, C, Cocca, M, Farmaki, A-E, Gaunt, TR, Jousilahti, P, Kooijman, MN, Lehne, B, Malerba, G, Männistö, S, Matchan, A, Medina-Gomez, C, Metrustry, SJ, Nag, A, Ntalla, I, Paternoster, L, Rayner, NW, Sala, C, Scott, WR, Shihab, HA, Southam, L, St Pourcain, B, Traglia, M, Trajanoska, K, Zaza, G, Zhang, W, Artigas, MS, Bansal, N, Benn, M, Chen, Z, Danecek, P, Lin, W-Y, Locke, AE, Luan, J, Manning, AK, Mulas, A, Sidore, C, Tybjaerg-Hansen, A, Nordestgaard, BG & SpiroMeta Consortium 2017, 'Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits', American Journal of Human Genetics, bind 100, nr. 6, s. 865-884. https://doi.org/10.1016/j.ajhg.2017.04.014

APA

Tachmazidou, I., Süveges, D., Min, J. L., Ritchie, G. R. S., Steinberg, J., Walter, K., Iotchkova, V., Schwartzentruber, J., Huang, J., Memari, Y., McCarthy, S., Crawford, A. J., Bombieri, C., Cocca, M., Farmaki, A-E., Gaunt, T. R., Jousilahti, P., Kooijman, M. N., Lehne, B., ... SpiroMeta Consortium (2017). Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits. American Journal of Human Genetics, 100(6), 865-884. https://doi.org/10.1016/j.ajhg.2017.04.014

Vancouver

Tachmazidou I, Süveges D, Min JL, Ritchie GRS, Steinberg J, Walter K o.a. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits. American Journal of Human Genetics. 2017 jun. 1;100(6):865-884. https://doi.org/10.1016/j.ajhg.2017.04.014

Author

Tachmazidou, Ioanna ; Süveges, Dániel ; Min, Josine L ; Ritchie, Graham R S ; Steinberg, Julia ; Walter, Klaudia ; Iotchkova, Valentina ; Schwartzentruber, Jeremy ; Huang, Jie ; Memari, Yasin ; McCarthy, Shane ; Crawford, Andrew J. ; Bombieri, Cristina ; Cocca, Massimiliano ; Farmaki, Aliki-Eleni ; Gaunt, Tom R ; Jousilahti, Pekka ; Kooijman, Marjolein N ; Lehne, Benjamin ; Malerba, Giovanni ; Männistö, Satu ; Matchan, Angela ; Medina-Gomez, Carolina ; Metrustry, Sarah J ; Nag, Abhishek ; Ntalla, Ioanna ; Paternoster, Lavinia ; Rayner, Nigel W ; Sala, Cinzia ; Scott, William R ; Shihab, Hashem A. ; Southam, Lorraine ; St Pourcain, Beate ; Traglia, Michela ; Trajanoska, Katerina ; Zaza, Gialuigi ; Zhang, Weihua ; Artigas, Maria Soler ; Bansal, Narinder ; Benn, Marianne ; Chen, Zhongsheng ; Danecek, Petr ; Lin, Wei-Yu ; Locke, Adam E ; Luan, Jian'an ; Manning, Alisa K ; Mulas, Antonella ; Sidore, Carlo ; Tybjaerg-Hansen, Anne ; Nordestgaard, Børge G ; SpiroMeta Consortium. / Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits. I: American Journal of Human Genetics. 2017 ; Bind 100, Nr. 6. s. 865-884.

Bibtex

@article{09620811b442407abb78788f91155b90,

title = "Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits",

abstract = "Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.",

keywords = "Journal Article",

author = "Ioanna Tachmazidou and D{\'a}niel S{\"u}veges and Min, {Josine L} and Ritchie, {Graham R S} and Julia Steinberg and Klaudia Walter and Valentina Iotchkova and Jeremy Schwartzentruber and Jie Huang and Yasin Memari and Shane McCarthy and Crawford, {Andrew J.} and Cristina Bombieri and Massimiliano Cocca and Aliki-Eleni Farmaki and Gaunt, {Tom R} and Pekka Jousilahti and Kooijman, {Marjolein N} and Benjamin Lehne and Giovanni Malerba and Satu M{\"a}nnist{\"o} and Angela Matchan and Carolina Medina-Gomez and Metrustry, {Sarah J} and Abhishek Nag and Ioanna Ntalla and Lavinia Paternoster and Rayner, {Nigel W} and Cinzia Sala and Scott, {William R} and Shihab, {Hashem A.} and Lorraine Southam and {St Pourcain}, Beate and Michela Traglia and Katerina Trajanoska and Gialuigi Zaza and Weihua Zhang and Artigas, {Maria Soler} and Narinder Bansal and Marianne Benn and Zhongsheng Chen and Petr Danecek and Wei-Yu Lin and Locke, {Adam E} and Jian'an Luan and Manning, {Alisa K} and Antonella Mulas and Carlo Sidore and Anne Tybjaerg-Hansen and Nordestgaard, {B{\o}rge G} and {SpiroMeta Consortium}",

year = "2017",

month = jun,

day = "1",

doi = "10.1016/j.ajhg.2017.04.014",

language = "English",

volume = "100",

pages = "865--884",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "6",

}

RIS

TY - JOUR

T1 - Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

AU - Tachmazidou, Ioanna

AU - Süveges, Dániel

AU - Min, Josine L

AU - Ritchie, Graham R S

AU - Steinberg, Julia

AU - Walter, Klaudia

AU - Iotchkova, Valentina

AU - Schwartzentruber, Jeremy

AU - Huang, Jie

AU - Memari, Yasin

AU - McCarthy, Shane

AU - Crawford, Andrew J.

AU - Bombieri, Cristina

AU - Cocca, Massimiliano

AU - Farmaki, Aliki-Eleni

AU - Gaunt, Tom R

AU - Jousilahti, Pekka

AU - Kooijman, Marjolein N

AU - Lehne, Benjamin

AU - Malerba, Giovanni

AU - Männistö, Satu

AU - Matchan, Angela

AU - Medina-Gomez, Carolina

AU - Metrustry, Sarah J

AU - Nag, Abhishek

AU - Ntalla, Ioanna

AU - Paternoster, Lavinia

AU - Rayner, Nigel W

AU - Sala, Cinzia

AU - Scott, William R

AU - Shihab, Hashem A.

AU - Southam, Lorraine

AU - St Pourcain, Beate

AU - Traglia, Michela

AU - Trajanoska, Katerina

AU - Zaza, Gialuigi

AU - Zhang, Weihua

AU - Artigas, Maria Soler

AU - Bansal, Narinder

AU - Benn, Marianne

AU - Chen, Zhongsheng

AU - Danecek, Petr

AU - Lin, Wei-Yu

AU - Locke, Adam E

AU - Luan, Jian'an

AU - Manning, Alisa K

AU - Mulas, Antonella

AU - Sidore, Carlo

AU - Tybjaerg-Hansen, Anne

AU - Nordestgaard, Børge G

AU - SpiroMeta Consortium

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.

AB - Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.

KW - Journal Article

U2 - 10.1016/j.ajhg.2017.04.014

DO - 10.1016/j.ajhg.2017.04.014

M3 - Journal article

C2 - 28552196

VL - 100

SP - 865

EP - 884

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 6

ER -

ID: 179406508

Institut for Klinisk Medicin