Weighting sequence variants based on their annotation increases power of whole-genome association studies

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

Standard

Weighting sequence variants based on their annotation increases power of whole-genome association studies. / Sveinbjornsson, Gardar; Albrechtsen, Anders; Zink, Florian; Gudjonsson, Sigurjón A.; Oddson, Asmundur; Másson, Gísli; Holm, Hilma; Kong, Augustine; Thorsteinsdottir, Unnur; Sulem, Patrick; Gudbjartsson, Daniel F.; Stefansson, Kari.

In: Nature Genetics, Vol. 48, No. 3, 2016, p. 314-317.

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

Harvard

Sveinbjornsson, G, Albrechtsen, A, Zink, F, Gudjonsson, SA, Oddson, A, Másson, G, Holm, H, Kong, A, Thorsteinsdottir, U, Sulem, P, Gudbjartsson, DF & Stefansson, K 2016, 'Weighting sequence variants based on their annotation increases power of whole-genome association studies', Nature Genetics, vol. 48, no. 3, pp. 314-317. https://doi.org/10.1038/ng.3507

APA

Sveinbjornsson, G., Albrechtsen, A., Zink, F., Gudjonsson, S. A., Oddson, A., Másson, G., Holm, H., Kong, A., Thorsteinsdottir, U., Sulem, P., Gudbjartsson, D. F., & Stefansson, K. (2016). Weighting sequence variants based on their annotation increases power of whole-genome association studies. Nature Genetics, 48(3), 314-317. https://doi.org/10.1038/ng.3507

Vancouver

Sveinbjornsson G, Albrechtsen A, Zink F, Gudjonsson SA, Oddson A, Másson G et al. Weighting sequence variants based on their annotation increases power of whole-genome association studies. Nature Genetics. 2016;48(3):314-317. https://doi.org/10.1038/ng.3507

Author

Sveinbjornsson, Gardar ; Albrechtsen, Anders ; Zink, Florian ; Gudjonsson, Sigurjón A. ; Oddson, Asmundur ; Másson, Gísli ; Holm, Hilma ; Kong, Augustine ; Thorsteinsdottir, Unnur ; Sulem, Patrick ; Gudbjartsson, Daniel F. ; Stefansson, Kari. / Weighting sequence variants based on their annotation increases power of whole-genome association studies. In: Nature Genetics. 2016 ; Vol. 48, No. 3. pp. 314-317.

Bibtex

@article{0cf89fc3b9764840b5c0c569e18b36a2,
title = "Weighting sequence variants based on their annotation increases power of whole-genome association studies",
abstract = "The consensus approach to genome-wide association studies (GWAS) has been to assign equal prior probability of association to all sequence variants tested. However, some sequence variants, such as loss-of-function and missense variants, are more likely than others to affect protein function and are therefore more likely to be causative. Using data from whole-genome sequencing of 2,636 Icelanders and the association results for 96 quantitative and 123 binary phenotypes, we estimated the enrichment of association signals by sequence annotation. We propose a weighted Bonferroni adjustment that controls for the family-wise error rate (FWER), using as weights the enrichment of sequence annotations among association signals. We show that this weighted adjustment increases the power to detect association over the standard Bonferroni correction. We use the enrichment of associations by sequence annotation we have estimated in Iceland to derive significance thresholds for other populations with different numbers and combinations of sequence variants.",
author = "Gardar Sveinbjornsson and Anders Albrechtsen and Florian Zink and Gudjonsson, {Sigurj{\'o}n A.} and Asmundur Oddson and G{\'i}sli M{\'a}sson and Hilma Holm and Augustine Kong and Unnur Thorsteinsdottir and Patrick Sulem and Gudbjartsson, {Daniel F.} and Kari Stefansson",
year = "2016",
doi = "10.1038/ng.3507",
language = "English",
volume = "48",
pages = "314--317",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "3",

}

RIS

TY - JOUR

T1 - Weighting sequence variants based on their annotation increases power of whole-genome association studies

AU - Sveinbjornsson, Gardar

AU - Albrechtsen, Anders

AU - Zink, Florian

AU - Gudjonsson, Sigurjón A.

AU - Oddson, Asmundur

AU - Másson, Gísli

AU - Holm, Hilma

AU - Kong, Augustine

AU - Thorsteinsdottir, Unnur

AU - Sulem, Patrick

AU - Gudbjartsson, Daniel F.

AU - Stefansson, Kari

PY - 2016

Y1 - 2016

N2 - The consensus approach to genome-wide association studies (GWAS) has been to assign equal prior probability of association to all sequence variants tested. However, some sequence variants, such as loss-of-function and missense variants, are more likely than others to affect protein function and are therefore more likely to be causative. Using data from whole-genome sequencing of 2,636 Icelanders and the association results for 96 quantitative and 123 binary phenotypes, we estimated the enrichment of association signals by sequence annotation. We propose a weighted Bonferroni adjustment that controls for the family-wise error rate (FWER), using as weights the enrichment of sequence annotations among association signals. We show that this weighted adjustment increases the power to detect association over the standard Bonferroni correction. We use the enrichment of associations by sequence annotation we have estimated in Iceland to derive significance thresholds for other populations with different numbers and combinations of sequence variants.

AB - The consensus approach to genome-wide association studies (GWAS) has been to assign equal prior probability of association to all sequence variants tested. However, some sequence variants, such as loss-of-function and missense variants, are more likely than others to affect protein function and are therefore more likely to be causative. Using data from whole-genome sequencing of 2,636 Icelanders and the association results for 96 quantitative and 123 binary phenotypes, we estimated the enrichment of association signals by sequence annotation. We propose a weighted Bonferroni adjustment that controls for the family-wise error rate (FWER), using as weights the enrichment of sequence annotations among association signals. We show that this weighted adjustment increases the power to detect association over the standard Bonferroni correction. We use the enrichment of associations by sequence annotation we have estimated in Iceland to derive significance thresholds for other populations with different numbers and combinations of sequence variants.

U2 - 10.1038/ng.3507

DO - 10.1038/ng.3507

M3 - Letter

C2 - 26854916

VL - 48

SP - 314

EP - 317

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -

ID: 160481281