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Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH

Li, Josephine H. ; Brenner, Laura N. ; Kaur, Varinderpal ; [weitere]

Springer Science and Business Media LLC ; 2023

In: Diabetologia Vol. 66, No. 7 ( 2023-07), p. 1260-1272

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In: Diabetologia, Springer Science and Business Media LLC, Vol. 66, No. 7 ( 2023-07), p. 1260-1272

Materialart: Online-Ressource

ISSN: 0012-186X , 1432-0428

URL: Article

DOI: 10.1007/s00125-023-05922-7

RVK:

XA 40615

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2023

ZDB Id: 1458993-X

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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Pattaro, Cristian ; Teumer, Alexander ; Gorski, Mathias ; [weitere]

Springer Science and Business Media LLC ; 2016

In: Nature Communications Vol. 7, No. 1 ( 2016-01-21)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-01-21)

Kurzfassung: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Materialart: Online-Ressource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/ncomms10023

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2016

ZDB Id: 2553671-0

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Author Correction: The power of genetic diversity in genome-wide association studies of lipids

Graham, Sarah E. ; Clarke, Shoa L. ; Wu, Kuan-Han H. ; [weitere]

Springer Science and Business Media LLC ; 2023

In: Nature Vol. 618, No. 7965 ( 2023-06-15), p. E19-E20

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In: Nature, Springer Science and Business Media LLC, Vol. 618, No. 7965 ( 2023-06-15), p. E19-E20

Materialart: Online-Ressource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-023-06194-2

RVK:

TA 1000

RVK:

UA 1000

RVK:

WA 15000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2023

ZDB Id: 120714-3

ZDB Id: 1413423-8

SSG: 11

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The trans-ancestral genomic architecture of glycemic traits

Chen, Ji ; Spracklen, Cassandra N. ; Marenne, Gaëlle ; [weitere]

Springer Science and Business Media LLC ; 2021

In: Nature Genetics Vol. 53, No. 6 ( 2021-06), p. 840-860

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In: Nature Genetics, Springer Science and Business Media LLC, Vol. 53, No. 6 ( 2021-06), p. 840-860

Materialart: Online-Ressource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/s41588-021-00852-9

RVK:

XA 10000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2021

ZDB Id: 1494946-5

SSG: 12

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The power of genetic diversity in genome-wide association studies of lipids

Graham, Sarah E. ; Clarke, Shoa L. ; Wu, Kuan-Han H. ; [weitere]

Springer Science and Business Media LLC ; 2021

In: Nature Vol. 600, No. 7890 ( 2021-12-23), p. 675-679

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In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7890 ( 2021-12-23), p. 675-679

Materialart: Online-Ressource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-021-04064-3

RVK:

TA 1000

RVK:

UA 1000

RVK:

WA 15000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2021

ZDB Id: 120714-3

ZDB Id: 1413423-8

SSG: 11

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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Kanoni, Stavroula ; Graham, Sarah E. ; Wang, Yuxuan ; [weitere]

Springer Science and Business Media LLC ; 2022

In: Genome Biology Vol. 23, No. 1 ( 2022-12-27)

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In: Genome Biology, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12-27)

Kurzfassung: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis ( N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Materialart: Online-Ressource

ISSN: 1474-760X

URL: Article

DOI: 10.1186/s13059-022-02837-1

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2022

ZDB Id: 2040529-7

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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

Ramdas, Shweta ; Judd, Jonathan ; Graham, Sarah E. ; [weitere]

Elsevier BV ; 2022

In: The American Journal of Human Genetics Vol. 109, No. 8 ( 2022-08), p. 1366-1387

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In: The American Journal of Human Genetics, Elsevier BV, Vol. 109, No. 8 ( 2022-08), p. 1366-1387

Materialart: Online-Ressource

ISSN: 0002-9297

URL: Article

DOI: 10.1016/j.ajhg.2022.06.012

RVK:

XA 10000

Sprache: Englisch

Verlag: Elsevier BV

Publikationsdatum: 2022

ZDB Id: 1473813-2

SSG: 12

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A catalog of genetic loci associated with kidney function from analyses of a million individuals

Wuttke, Matthias ; Lifelines Cohort Study ; Li, Yong ; [weitere]

Springer Science and Business Media LLC ; 2019

In: Nature Genetics Vol. 51, No. 6 ( 2019-6), p. 957-972

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In: Nature Genetics, Springer Science and Business Media LLC, Vol. 51, No. 6 ( 2019-6), p. 957-972

Materialart: Online-Ressource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/s41588-019-0407-x

RVK:

XA 10000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2019

ZDB Id: 1494946-5

SSG: 12

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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Wheeler, Eleanor ; Leong, Aaron ; Liu, Ching-Ti ; [weitere]

Public Library of Science (PLoS) ; 2017

In: PLOS Medicine Vol. 14, No. 9 ( 2017-9-12), p. e1002383-

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In: PLOS Medicine, Public Library of Science (PLoS), Vol. 14, No. 9 ( 2017-9-12), p. e1002383-

Materialart: Online-Ressource

ISSN: 1549-1676

URL: Article

DOI: 10.1371/journal.pmed.1002383

DOI: 10.1371/journal.pmed.1002383.g001

DOI: 10.1371/journal.pmed.1002383.g002

DOI: 10.1371/journal.pmed.1002383.g003

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DOI: 10.1371/journal.pmed.1002383.t001

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DOI: 10.1371/journal.pmed.1002383.s001

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DOI: 10.1371/journal.pmed.1002383.s010

DOI: 10.1371/journal.pmed.1002383.s011

DOI: 10.1371/journal.pmed.1002383.s012

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DOI: 10.1371/journal.pmed.1002383.s017

DOI: 10.1371/journal.pmed.1002383.s018

DOI: 10.1371/journal.pmed.1002383.s019

Sprache: Englisch

Verlag: Public Library of Science (PLoS)

Publikationsdatum: 2017

ZDB Id: 2164823-2

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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Feitosa, Mary F. ; Kraja, Aldi T. ; Chasman, Daniel I. ; [weitere]

Public Library of Science (PLoS) ; 2018

In: PLOS ONE Vol. 13, No. 6 ( 2018-6-18), p. e0198166-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 13, No. 6 ( 2018-6-18), p. e0198166-

Materialart: Online-Ressource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0198166

DOI: 10.1371/journal.pone.0198166.g001

DOI: 10.1371/journal.pone.0198166.t001

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DOI: 10.1371/journal.pone.0198166.s035

Sprache: Englisch

Verlag: Public Library of Science (PLoS)

Publikationsdatum: 2018

ZDB Id: 2267670-3

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