Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Research output: Contribution to journalJournal articlepeer-review

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Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes. / Bonàs-Guarch, Sílvia; Guindo-Martínez, Marta; Miguel-Escalada, Irene; Grarup, Niels; Sebastian, David; Rodriguez-Fos, Elias; Sánchez, Friman; Planas-Fèlix, Mercè; Cortes-Sánchez, Paula; González, Santi; Timshel, Pascal; Pers, Tune H; Morgan, Claire C; Moran, Ignasi; Atla, Goutham; González, Juan R; Puiggros, Montserrat; Martí, Jonathan; Andersson, Ehm A; Díaz, Carlos; Badia, Rosa M; Udler, Miriam; Leong, Aaron; Kaur, Varindepal; Flannick, Jason; Jørgensen, Torben; Linneberg, Allan; Jørgensen, Marit E; Witte, Daniel R; Christensen, Cramer; Brandslund, Ivan; Appel, Emil V; Scott, Robert A; Luan, Jian'an; Langenberg, Claudia; Wareham, Nicholas J; Pedersen, Oluf; Zorzano, Antonio; Florez, Jose C; Hansen, Torben; Ferrer, Jorge; Mercader, Josep Maria; Torrents, David.

In: Nature Communications, Vol. 9, 321, 22.01.2018.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Bonàs-Guarch, S, Guindo-Martínez, M, Miguel-Escalada, I, Grarup, N, Sebastian, D, Rodriguez-Fos, E, Sánchez, F, Planas-Fèlix, M, Cortes-Sánchez, P, González, S, Timshel, P, Pers, TH, Morgan, CC, Moran, I, Atla, G, González, JR, Puiggros, M, Martí, J, Andersson, EA, Díaz, C, Badia, RM, Udler, M, Leong, A, Kaur, V, Flannick, J, Jørgensen, T, Linneberg, A, Jørgensen, ME, Witte, DR, Christensen, C, Brandslund, I, Appel, EV, Scott, RA, Luan, J, Langenberg, C, Wareham, NJ, Pedersen, O, Zorzano, A, Florez, JC, Hansen, T, Ferrer, J, Mercader, JM & Torrents, D 2018, 'Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes', Nature Communications, vol. 9, 321. https://doi.org/10.1038/s41467-017-02380-9

APA

Bonàs-Guarch, S., Guindo-Martínez, M., Miguel-Escalada, I., Grarup, N., Sebastian, D., Rodriguez-Fos, E., Sánchez, F., Planas-Fèlix, M., Cortes-Sánchez, P., González, S., Timshel, P., Pers, T. H., Morgan, C. C., Moran, I., Atla, G., González, J. R., Puiggros, M., Martí, J., Andersson, E. A., ... Torrents, D. (2018). Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes. Nature Communications, 9, [321]. https://doi.org/10.1038/s41467-017-02380-9

Vancouver

Bonàs-Guarch S, Guindo-Martínez M, Miguel-Escalada I, Grarup N, Sebastian D, Rodriguez-Fos E et al. Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes. Nature Communications. 2018 Jan 22;9. 321. https://doi.org/10.1038/s41467-017-02380-9

Author

Bonàs-Guarch, Sílvia ; Guindo-Martínez, Marta ; Miguel-Escalada, Irene ; Grarup, Niels ; Sebastian, David ; Rodriguez-Fos, Elias ; Sánchez, Friman ; Planas-Fèlix, Mercè ; Cortes-Sánchez, Paula ; González, Santi ; Timshel, Pascal ; Pers, Tune H ; Morgan, Claire C ; Moran, Ignasi ; Atla, Goutham ; González, Juan R ; Puiggros, Montserrat ; Martí, Jonathan ; Andersson, Ehm A ; Díaz, Carlos ; Badia, Rosa M ; Udler, Miriam ; Leong, Aaron ; Kaur, Varindepal ; Flannick, Jason ; Jørgensen, Torben ; Linneberg, Allan ; Jørgensen, Marit E ; Witte, Daniel R ; Christensen, Cramer ; Brandslund, Ivan ; Appel, Emil V ; Scott, Robert A ; Luan, Jian'an ; Langenberg, Claudia ; Wareham, Nicholas J ; Pedersen, Oluf ; Zorzano, Antonio ; Florez, Jose C ; Hansen, Torben ; Ferrer, Jorge ; Mercader, Josep Maria ; Torrents, David. / Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes. In: Nature Communications. 2018 ; Vol. 9.

Bibtex

@article{7dc5909e082344b2a7c0d841ebb2189f,
title = "Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes",
abstract = "The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.",
keywords = "Journal Article",
author = "S{\'i}lvia Bon{\`a}s-Guarch and Marta Guindo-Mart{\'i}nez and Irene Miguel-Escalada and Niels Grarup and David Sebastian and Elias Rodriguez-Fos and Friman S{\'a}nchez and Merc{\`e} Planas-F{\`e}lix and Paula Cortes-S{\'a}nchez and Santi Gonz{\'a}lez and Pascal Timshel and Pers, {Tune H} and Morgan, {Claire C} and Ignasi Moran and Goutham Atla and Gonz{\'a}lez, {Juan R} and Montserrat Puiggros and Jonathan Mart{\'i} and Andersson, {Ehm A} and Carlos D{\'i}az and Badia, {Rosa M} and Miriam Udler and Aaron Leong and Varindepal Kaur and Jason Flannick and Torben J{\o}rgensen and Allan Linneberg and J{\o}rgensen, {Marit E} and Witte, {Daniel R} and Cramer Christensen and Ivan Brandslund and Appel, {Emil V} and Scott, {Robert A} and Jian'an Luan and Claudia Langenberg and Wareham, {Nicholas J} and Oluf Pedersen and Antonio Zorzano and Florez, {Jose C} and Torben Hansen and Jorge Ferrer and Mercader, {Josep Maria} and David Torrents",
year = "2018",
month = jan,
day = "22",
doi = "10.1038/s41467-017-02380-9",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

AU - Bonàs-Guarch, Sílvia

AU - Guindo-Martínez, Marta

AU - Miguel-Escalada, Irene

AU - Grarup, Niels

AU - Sebastian, David

AU - Rodriguez-Fos, Elias

AU - Sánchez, Friman

AU - Planas-Fèlix, Mercè

AU - Cortes-Sánchez, Paula

AU - González, Santi

AU - Timshel, Pascal

AU - Pers, Tune H

AU - Morgan, Claire C

AU - Moran, Ignasi

AU - Atla, Goutham

AU - González, Juan R

AU - Puiggros, Montserrat

AU - Martí, Jonathan

AU - Andersson, Ehm A

AU - Díaz, Carlos

AU - Badia, Rosa M

AU - Udler, Miriam

AU - Leong, Aaron

AU - Kaur, Varindepal

AU - Flannick, Jason

AU - Jørgensen, Torben

AU - Linneberg, Allan

AU - Jørgensen, Marit E

AU - Witte, Daniel R

AU - Christensen, Cramer

AU - Brandslund, Ivan

AU - Appel, Emil V

AU - Scott, Robert A

AU - Luan, Jian'an

AU - Langenberg, Claudia

AU - Wareham, Nicholas J

AU - Pedersen, Oluf

AU - Zorzano, Antonio

AU - Florez, Jose C

AU - Hansen, Torben

AU - Ferrer, Jorge

AU - Mercader, Josep Maria

AU - Torrents, David

PY - 2018/1/22

Y1 - 2018/1/22

N2 - The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.

AB - The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.

KW - Journal Article

UR - https://www.nature.com/articles/s41467-018-04170-3.pdf

U2 - 10.1038/s41467-017-02380-9

DO - 10.1038/s41467-017-02380-9

M3 - Journal article

C2 - 29358691

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 321

ER -

ID: 189767358