Standard
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. / Gaulton, Kyle J; Ferreira, Teresa; Lee, Yeji; Raimondo, Anne; Mägi, Reedik; Reschen, Michael E; Mahajan, Anubha; Locke, Adam; William Rayner, N; Robertson, Neil; Scott, Robert A; Prokopenko, Inga; Scott, Laura J; Green, Todd; Sparso, Thomas; Thuillier, Dorothee; Yengo, Loic; Grallert, Harald; Wahl, Simone; Frånberg, Mattias; Strawbridge, Rona J; Kestler, Hans; Chheda, Himanshu; Eisele, Lewin; Gustafsson, Stefan; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Qi, Lu; Karssen, Lennart C; van Leeuwen, Elisabeth M; Willems, Sara M; Li, Man; Chen, Han; Fuchsberger, Christian; Kwan, Phoenix; Ma, Clement; Linderman, Michael; Lu, Yingchang; Thomsen, Soren K; Rundle, Jana K; Grarup, Niels; Have, Christian T; Jonsson, Anna; Jørgensen, Marit Eika; Jørgensen, Torben; Linneberg, Allan; Storm, Petter; Njølstad, Inger; Hansen, Torben; Pedersen, Oluf; Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium.
In:
Nature Genetics, Vol. 47, No. 12, 12.2015, p. 1415-25, 3 unpag. pages.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Gaulton, KJ, Ferreira, T, Lee, Y, Raimondo, A, Mägi, R, Reschen, ME, Mahajan, A, Locke, A, William Rayner, N, Robertson, N, Scott, RA, Prokopenko, I, Scott, LJ, Green, T, Sparso, T, Thuillier, D, Yengo, L, Grallert, H, Wahl, S, Frånberg, M, Strawbridge, RJ, Kestler, H, Chheda, H, Eisele, L, Gustafsson, S, Steinthorsdottir, V, Thorleifsson, G, Qi, L, Karssen, LC, van Leeuwen, EM, Willems, SM, Li, M, Chen, H, Fuchsberger, C, Kwan, P, Ma, C, Linderman, M, Lu, Y, Thomsen, SK, Rundle, JK
, Grarup, N, Have, CT
, Jonsson, A, Jørgensen, ME, Jørgensen, T
, Linneberg, A, Storm, P, Njølstad, I
, Hansen, T, Pedersen, O & Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium 2015, '
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci',
Nature Genetics, vol. 47, no. 12, pp. 1415-25, 3 unpag. pages.
https://doi.org/10.1038/ng.3437APA
Gaulton, K. J., Ferreira, T., Lee, Y., Raimondo, A., Mägi, R., Reschen, M. E., Mahajan, A., Locke, A., William Rayner, N., Robertson, N., Scott, R. A., Prokopenko, I., Scott, L. J., Green, T., Sparso, T., Thuillier, D., Yengo, L., Grallert, H., Wahl, S., ... Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium (2015).
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
Nature Genetics,
47(12), 1415-25, 3 unpag. pages.
https://doi.org/10.1038/ng.3437Vancouver
Gaulton KJ, Ferreira T, Lee Y, Raimondo A, Mägi R, Reschen ME et al.
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
Nature Genetics. 2015 Dec;47(12):1415-25, 3 unpag. pages.
https://doi.org/10.1038/ng.3437Author
Gaulton, Kyle J ; Ferreira, Teresa ; Lee, Yeji ; Raimondo, Anne ; Mägi, Reedik ; Reschen, Michael E ; Mahajan, Anubha ; Locke, Adam ; William Rayner, N ; Robertson, Neil ; Scott, Robert A ; Prokopenko, Inga ; Scott, Laura J ; Green, Todd ; Sparso, Thomas ; Thuillier, Dorothee ; Yengo, Loic ; Grallert, Harald ; Wahl, Simone ; Frånberg, Mattias ; Strawbridge, Rona J ; Kestler, Hans ; Chheda, Himanshu ; Eisele, Lewin ; Gustafsson, Stefan ; Steinthorsdottir, Valgerdur ; Thorleifsson, Gudmar ; Qi, Lu ; Karssen, Lennart C ; van Leeuwen, Elisabeth M ; Willems, Sara M ; Li, Man ; Chen, Han ; Fuchsberger, Christian ; Kwan, Phoenix ; Ma, Clement ; Linderman, Michael ; Lu, Yingchang ; Thomsen, Soren K ; Rundle, Jana K ; Grarup, Niels ; Have, Christian T ; Jonsson, Anna ; Jørgensen, Marit Eika ; Jørgensen, Torben ; Linneberg, Allan ; Storm, Petter ; Njølstad, Inger ; Hansen, Torben ; Pedersen, Oluf ; Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. / Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. In: Nature Genetics. 2015 ; Vol. 47, No. 12. pp. 1415-25, 3 unpag. pages.
Bibtex
@article{34c8b577b9bc4f2e9e8007251f03e485,
title = "Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci",
abstract = "We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.",
author = "Gaulton, {Kyle J} and Teresa Ferreira and Yeji Lee and Anne Raimondo and Reedik M{\"a}gi and Reschen, {Michael E} and Anubha Mahajan and Adam Locke and {William Rayner}, N and Neil Robertson and Scott, {Robert A} and Inga Prokopenko and Scott, {Laura J} and Todd Green and Thomas Sparso and Dorothee Thuillier and Loic Yengo and Harald Grallert and Simone Wahl and Mattias Fr{\aa}nberg and Strawbridge, {Rona J} and Hans Kestler and Himanshu Chheda and Lewin Eisele and Stefan Gustafsson and Valgerdur Steinthorsdottir and Gudmar Thorleifsson and Lu Qi and Karssen, {Lennart C} and {van Leeuwen}, {Elisabeth M} and Willems, {Sara M} and Man Li and Han Chen and Christian Fuchsberger and Phoenix Kwan and Clement Ma and Michael Linderman and Yingchang Lu and Thomsen, {Soren K} and Rundle, {Jana K} and Niels Grarup and Have, {Christian T} and Anna Jonsson and J{\o}rgensen, {Marit Eika} and Torben J{\o}rgensen and Allan Linneberg and Petter Storm and Inger Nj{\o}lstad and Torben Hansen and Oluf Pedersen and {Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium}",
year = "2015",
month = dec,
doi = "10.1038/ng.3437",
language = "English",
volume = "47",
pages = "1415--25, 3 unpag. pages",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "12",
}
RIS
TY - JOUR
T1 - Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci
AU - Gaulton, Kyle J
AU - Ferreira, Teresa
AU - Lee, Yeji
AU - Raimondo, Anne
AU - Mägi, Reedik
AU - Reschen, Michael E
AU - Mahajan, Anubha
AU - Locke, Adam
AU - William Rayner, N
AU - Robertson, Neil
AU - Scott, Robert A
AU - Prokopenko, Inga
AU - Scott, Laura J
AU - Green, Todd
AU - Sparso, Thomas
AU - Thuillier, Dorothee
AU - Yengo, Loic
AU - Grallert, Harald
AU - Wahl, Simone
AU - Frånberg, Mattias
AU - Strawbridge, Rona J
AU - Kestler, Hans
AU - Chheda, Himanshu
AU - Eisele, Lewin
AU - Gustafsson, Stefan
AU - Steinthorsdottir, Valgerdur
AU - Thorleifsson, Gudmar
AU - Qi, Lu
AU - Karssen, Lennart C
AU - van Leeuwen, Elisabeth M
AU - Willems, Sara M
AU - Li, Man
AU - Chen, Han
AU - Fuchsberger, Christian
AU - Kwan, Phoenix
AU - Ma, Clement
AU - Linderman, Michael
AU - Lu, Yingchang
AU - Thomsen, Soren K
AU - Rundle, Jana K
AU - Grarup, Niels
AU - Have, Christian T
AU - Jonsson, Anna
AU - Jørgensen, Marit Eika
AU - Jørgensen, Torben
AU - Linneberg, Allan
AU - Storm, Petter
AU - Njølstad, Inger
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium
PY - 2015/12
Y1 - 2015/12
N2 - We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
AB - We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
U2 - 10.1038/ng.3437
DO - 10.1038/ng.3437
M3 - Journal article
C2 - 26551672
VL - 47
SP - 1415-25, 3 unpag. pages
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 12
ER -
