Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

Research output: Contribution to journalJournal articlepeer-review

Standard

Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics. / Lundby, Alicia; Rossin, Elizabeth J; Steffensen, Annette B; Acha, Moshe Rav; Newton-Cheh, Christopher; Pfeufer, Arne; Lynch, Stacey N; Olesen, Søren-Peter; Brunak, Søren; Ellinor, Patrick T; Jukema, J Wouter; Trompet, Stella; Ford, Ian; Macfarlane, Peter W; Krijthe, Bouwe P; Hofman, Albert; Uitterlinden, André G; Stricker, Bruno H; Nathoe, Hendrik M; Spiering, Wilko; Daly, Mark J; Asselbergs, Folkert W; van der Harst, Pim; Milan, David J; de Bakker, Paul I W; Hansen, Kasper Lage; Olsen, Jesper V; The QT Interval International GWAS Consortium (QT-IGC).

In: Nature Methods, Vol. 11, No. 8, 22.06.2014, p. 868-874.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Lundby, A, Rossin, EJ, Steffensen, AB, Acha, MR, Newton-Cheh, C, Pfeufer, A, Lynch, SN, Olesen, S-P, Brunak, S, Ellinor, PT, Jukema, JW, Trompet, S, Ford, I, Macfarlane, PW, Krijthe, BP, Hofman, A, Uitterlinden, AG, Stricker, BH, Nathoe, HM, Spiering, W, Daly, MJ, Asselbergs, FW, van der Harst, P, Milan, DJ, de Bakker, PIW, Hansen, KL, Olsen, JV & The QT Interval International GWAS Consortium (QT-IGC) 2014, 'Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics', Nature Methods, vol. 11, no. 8, pp. 868-874. https://doi.org/10.1038/nmeth.2997

APA

Lundby, A., Rossin, E. J., Steffensen, A. B., Acha, M. R., Newton-Cheh, C., Pfeufer, A., Lynch, S. N., Olesen, S-P., Brunak, S., Ellinor, P. T., Jukema, J. W., Trompet, S., Ford, I., Macfarlane, P. W., Krijthe, B. P., Hofman, A., Uitterlinden, A. G., Stricker, B. H., Nathoe, H. M., ... The QT Interval International GWAS Consortium (QT-IGC) (2014). Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics. Nature Methods, 11(8), 868-874. https://doi.org/10.1038/nmeth.2997

Vancouver

Lundby A, Rossin EJ, Steffensen AB, Acha MR, Newton-Cheh C, Pfeufer A et al. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics. Nature Methods. 2014 Jun 22;11(8):868-874. https://doi.org/10.1038/nmeth.2997

Author

Lundby, Alicia ; Rossin, Elizabeth J ; Steffensen, Annette B ; Acha, Moshe Rav ; Newton-Cheh, Christopher ; Pfeufer, Arne ; Lynch, Stacey N ; Olesen, Søren-Peter ; Brunak, Søren ; Ellinor, Patrick T ; Jukema, J Wouter ; Trompet, Stella ; Ford, Ian ; Macfarlane, Peter W ; Krijthe, Bouwe P ; Hofman, Albert ; Uitterlinden, André G ; Stricker, Bruno H ; Nathoe, Hendrik M ; Spiering, Wilko ; Daly, Mark J ; Asselbergs, Folkert W ; van der Harst, Pim ; Milan, David J ; de Bakker, Paul I W ; Hansen, Kasper Lage ; Olsen, Jesper V ; The QT Interval International GWAS Consortium (QT-IGC). / Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics. In: Nature Methods. 2014 ; Vol. 11, No. 8. pp. 868-874.

Bibtex

@article{bb1ba3df489c43b48ffb47031bdd988a,
title = "Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics",
abstract = "Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LQTS protein network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics.",
author = "Alicia Lundby and Rossin, {Elizabeth J} and Steffensen, {Annette B} and Acha, {Moshe Rav} and Christopher Newton-Cheh and Arne Pfeufer and Lynch, {Stacey N} and S{\o}ren-Peter Olesen and S{\o}ren Brunak and Ellinor, {Patrick T} and Jukema, {J Wouter} and Stella Trompet and Ian Ford and Macfarlane, {Peter W} and Krijthe, {Bouwe P} and Albert Hofman and Uitterlinden, {Andr{\'e} G} and Stricker, {Bruno H} and Nathoe, {Hendrik M} and Wilko Spiering and Daly, {Mark J} and Asselbergs, {Folkert W} and {van der Harst}, Pim and Milan, {David J} and {de Bakker}, {Paul I W} and Hansen, {Kasper Lage} and Olsen, {Jesper V} and {The QT Interval International GWAS Consortium (QT-IGC)}",
year = "2014",
month = jun,
day = "22",
doi = "10.1038/nmeth.2997",
language = "English",
volume = "11",
pages = "868--874",
journal = "Nature Methods",
issn = "1548-7091",
publisher = "nature publishing group",
number = "8",

}

RIS

TY - JOUR

T1 - Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

AU - Lundby, Alicia

AU - Rossin, Elizabeth J

AU - Steffensen, Annette B

AU - Acha, Moshe Rav

AU - Newton-Cheh, Christopher

AU - Pfeufer, Arne

AU - Lynch, Stacey N

AU - Olesen, Søren-Peter

AU - Brunak, Søren

AU - Ellinor, Patrick T

AU - Jukema, J Wouter

AU - Trompet, Stella

AU - Ford, Ian

AU - Macfarlane, Peter W

AU - Krijthe, Bouwe P

AU - Hofman, Albert

AU - Uitterlinden, André G

AU - Stricker, Bruno H

AU - Nathoe, Hendrik M

AU - Spiering, Wilko

AU - Daly, Mark J

AU - Asselbergs, Folkert W

AU - van der Harst, Pim

AU - Milan, David J

AU - de Bakker, Paul I W

AU - Hansen, Kasper Lage

AU - Olsen, Jesper V

AU - The QT Interval International GWAS Consortium (QT-IGC)

PY - 2014/6/22

Y1 - 2014/6/22

N2 - Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LQTS protein network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics.

AB - Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LQTS protein network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics.

U2 - 10.1038/nmeth.2997

DO - 10.1038/nmeth.2997

M3 - Journal article

C2 - 24952909

VL - 11

SP - 868

EP - 874

JO - Nature Methods

JF - Nature Methods

SN - 1548-7091

IS - 8

ER -

ID: 117564096