TIGER: The gene expression regulatory variation landscape of human pancreatic islets

被引：52

作者：

Alonso, Lorena ^{[1
]}

Piron, Anthony ^{[2
,3
]}

Moran, Ignasi ^{[1
]}

Guindo-Martinez, Marta ^{[1
]}

Bonas-Guarch, Silvia ^{[4
,5
]}

Atla, Goutham ^{[4
,5
]}

Miguel-Escalada, Irene ^{[4
,5
]}

Royo, Romina ^{[1
]}

Puiggros, Montserrat ^{[1
]}

Garcia-Hurtado, Xavier ^{[4
,5
]}

Suleiman, Mara ^{[6
,7
]}

Marselli, Lorella ^{[6
,7
]}

Esguerra, Jonathan L. S. ^{[8
]}

Turatsinze, Jean-Valery ^{[2
]}

Torres, Jason M. ^{[9
,10
,11
]}

Nylander, Vibe ^{[12
]}

Chen, Ji ^{[13
]}

Eliasson, Lena ^{[8
]}

Defrance, Matthieu ^{[2
]}

Amela, Ramon ^{[1
]}

Mulder, Hindrik ^{[14
]}

Gloyn, Anna L. ^{[11
,12
,15
,16
,17
]}

Groop, Leif ^{[8
,14
,18
]}

Marchetti, Piero ^{[6
,7
]}

Eizirik, Decio L. ^{[2
,19
]}

Ferrer, Jorge ^{[4
,5
,20
]}

Mercader, Josep M. ^{[1
,21
,22
,23
,24
,25
]}

Cnop, Miriam ^{[2
,26
]}

Torrents, David ^{[1
,27
]}

机构：

[1] Barcelona Supercomp Ctr BSC, Life Sci Dept, Barcelona 08034, Spain

[2] Univ Libre Bruxelles, ULB Ctr Diabet Res, B-1070 Brussels, Belgium

[3] Interuniv Inst Bioinformat Brussels IB2, B-1050 Brussels, Belgium

[4] Barcelona Inst Sci & Technol BIST, Ctr Genom Regulat CRG, Bioinformat & Genom Program, Barcelona 08003, Spain

[5] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona 08013, Spain

[6] Univ Pisa, Dept Clin & Expt Med, I-56126 Pisa, Italy

[7] Univ Pisa, AOUP Cisanello Univ Hosp, I-56126 Pisa, Italy

[8] Lund Univ, Diabet Ctr, Unit Islet Cell Exocytosis, S-21428 Malmo, Sweden

[9] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford OX3 7LF, England

[10] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England

[11] Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford OX3 7LF, England

[12] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford OX3 7LE, England

[13] Univ Exeter, Med Sch, Exeter Ctr Excellence Diabet Res EXCEED, Exeter EX4 4PY, Devon, England

[14] Lund Univ, Diabet Ctr, Unit Mol Metab, S-21428 Malmo, Sweden

[15] Stanford Univ, Sch Med, Dept Pediat, Div Endocrinol, Stanford, CA 94304 USA

[16] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7DQ, England

[17] Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA

[18] Univ Helsinki, Finnish Inst Mol Med Finland FIMM, Helsinki 00014, Finland

[19] Univ Libre Bruxelles, WELBIO, B-1050 Brussels, Belgium

[20] Imperial Coll London, Dept Med, Sect Epigen & Dis, London SW7 2AZ, England

[21] Broad Inst Harvard & MIT, Programs Metab, Cambridge, MA 02142 USA

[22] Broad Inst Harvard & MIT, Programs Med & Populat Genet, Cambridge, MA 02142 USA

[23] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA

[24] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[25] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[26] Univ Libre Bruxelles, Erasmus Hosp, Div Endocrinol, B-1070 Brussels, Belgium

[27] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona 08010, Spain

来源：

CELL REPORTS | 2021年 / 37卷 / 02期

基金：

英国惠康基金; 英国医学研究理事会; 欧洲研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; PANCREATECTOMIZED PATIENTS; PROVIDES INSIGHTS; READ ALIGNMENT; CHROMATIN; RISK; SECRETION; VARIANTS; BIOBANK; DESIGN;

D O I：

10.1016/j.celrep.2021.109807

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.

引用

页数：22

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