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Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes

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Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes. / Wallace, Chris; Rotival, Maxime; Cooper, Jason D; Rice, Catherine M; Yang, Jennie H M; McNeill, Mhairi; Smyth, Deborah J; Niblett, David; Cambien, François; Tiret, Laurence; Todd, John A; Clayton, David G; Blankenberg, Stefan; CardioGenics Consortium.

In: HUM MOL GENET, Vol. 21, No. 12, 15.06.2012, p. 2815-2824.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wallace, C, Rotival, M, Cooper, JD, Rice, CM, Yang, JHM, McNeill, M, Smyth, DJ, Niblett, D, Cambien, F, Tiret, L, Todd, JA, Clayton, DG, Blankenberg, S & CardioGenics Consortium 2012, 'Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes', HUM MOL GENET, vol. 21, no. 12, pp. 2815-2824. https://doi.org/10.1093/hmg/dds098

APA

Wallace, C., Rotival, M., Cooper, J. D., Rice, C. M., Yang, J. H. M., McNeill, M., Smyth, D. J., Niblett, D., Cambien, F., Tiret, L., Todd, J. A., Clayton, D. G., Blankenberg, S., & CardioGenics Consortium (2012). Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes. HUM MOL GENET, 21(12), 2815-2824. https://doi.org/10.1093/hmg/dds098

Vancouver

Wallace C, Rotival M, Cooper JD, Rice CM, Yang JHM, McNeill M et al. Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes. HUM MOL GENET. 2012 Jun 15;21(12):2815-2824. https://doi.org/10.1093/hmg/dds098

Bibtex

@article{611de2c4d7774cfe8a8f7e5cbf9e6e3c,
title = "Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes",
abstract = "One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1370 individuals), with confirmation sought in an additional data set from the Cardiogenics Transcriptome Study (558 individuals). We excluded 39 out of 60 overlapping eQTLs in 49 T1D regions from possible colocalization and identified 21 coincident eQTLs, representing 21 genes in 14 distinct T1D regions. Our results reflect the importance of monocyte (and their derivatives, macrophage and dendritic cell) gene expression in human T1D and support the candidacy of several genes as causal factors in autoimmune pancreatic beta-cell destruction, including AFF3, CD226, CLECL1, DEXI, FKRP, PRKD2, RNLS, SMARCE1 and SUOX, in addition to the recently described GPR183 (EBI2) gene.",
keywords = "Adult, Aged, Algorithms, Diabetes Mellitus, Type 1/genetics, Female, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Male, Middle Aged, Models, Genetic, Monocytes/metabolism, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics, Risk Factors, Transcriptome",
author = "Chris Wallace and Maxime Rotival and Cooper, {Jason D} and Rice, {Catherine M} and Yang, {Jennie H M} and Mhairi McNeill and Smyth, {Deborah J} and David Niblett and Fran{\c c}ois Cambien and Laurence Tiret and Todd, {John A} and Clayton, {David G} and Stefan Blankenberg and {CardioGenics Consortium}",
year = "2012",
month = jun,
day = "15",
doi = "10.1093/hmg/dds098",
language = "English",
volume = "21",
pages = "2815--2824",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes

AU - Wallace, Chris

AU - Rotival, Maxime

AU - Cooper, Jason D

AU - Rice, Catherine M

AU - Yang, Jennie H M

AU - McNeill, Mhairi

AU - Smyth, Deborah J

AU - Niblett, David

AU - Cambien, François

AU - Tiret, Laurence

AU - Todd, John A

AU - Clayton, David G

AU - Blankenberg, Stefan

AU - CardioGenics Consortium

PY - 2012/6/15

Y1 - 2012/6/15

N2 - One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1370 individuals), with confirmation sought in an additional data set from the Cardiogenics Transcriptome Study (558 individuals). We excluded 39 out of 60 overlapping eQTLs in 49 T1D regions from possible colocalization and identified 21 coincident eQTLs, representing 21 genes in 14 distinct T1D regions. Our results reflect the importance of monocyte (and their derivatives, macrophage and dendritic cell) gene expression in human T1D and support the candidacy of several genes as causal factors in autoimmune pancreatic beta-cell destruction, including AFF3, CD226, CLECL1, DEXI, FKRP, PRKD2, RNLS, SMARCE1 and SUOX, in addition to the recently described GPR183 (EBI2) gene.

AB - One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1370 individuals), with confirmation sought in an additional data set from the Cardiogenics Transcriptome Study (558 individuals). We excluded 39 out of 60 overlapping eQTLs in 49 T1D regions from possible colocalization and identified 21 coincident eQTLs, representing 21 genes in 14 distinct T1D regions. Our results reflect the importance of monocyte (and their derivatives, macrophage and dendritic cell) gene expression in human T1D and support the candidacy of several genes as causal factors in autoimmune pancreatic beta-cell destruction, including AFF3, CD226, CLECL1, DEXI, FKRP, PRKD2, RNLS, SMARCE1 and SUOX, in addition to the recently described GPR183 (EBI2) gene.

KW - Adult

KW - Aged

KW - Algorithms

KW - Diabetes Mellitus, Type 1/genetics

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Linkage Disequilibrium

KW - Male

KW - Middle Aged

KW - Models, Genetic

KW - Monocytes/metabolism

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci/genetics

KW - Risk Factors

KW - Transcriptome

U2 - 10.1093/hmg/dds098

DO - 10.1093/hmg/dds098

M3 - SCORING: Journal article

C2 - 22403184

VL - 21

SP - 2815

EP - 2824

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 12

ER -