PuSH - Publikationsserver des Helmholtz Zentrums München: A novel splice-affecting <em>HNF1A</em> variant with large population impact on diabetes in Greenland.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Thuesen, A.C.B.* ; Stæger, F.F.* ; Kaci, A.* ; Solheim, M.H.* ; Aukrust, I.* ; Jørsboe, E.* ; Santander, C.G.* ; Andersen, M.K.* ; Li, Z.* ; Gilly, A. ; Stinson, S.E.* ; Gjesing, A.P.* ; Bjerregaard, P.* ; Pedersen, M.L.* ; Larsen, C.V.L.* ; Grarup, N.* ; Jørgensen, M.E.* ; Zeggini, E. ; Bjørkhaug, L.* ; Njølstad, P.R.* ; Albrechtsen, A.* ; Moltke, I.* ; Hansen, T.*

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland.

Lancet Reg. Health-Eur. 24:100529 (2023)

Verlagsversion

DOI

PMC

	Open Access Gold

Abstract
Metriken
Zusatzinfos

Background: The genetic disease architecture of Inuit includes a large number of common high-impact variants. Identification of such variants contributes to our understanding of the genetic aetiology of diseases and improves global equity in genomic personalised medicine. We aimed to identify and characterise novel variants in genes associated with Maturity Onset Diabetes of the Young (MODY) in the Greenlandic population. Methods: Using combined data from Greenlandic population cohorts of 4497 individuals, including 448 whole genome sequenced individuals, we screened 14 known MODY genes for previously identified and novel variants. We functionally characterised an identified novel variant and assessed its association with diabetes prevalence and cardiometabolic traits and population impact. Findings: We identified a novel variant in the known MODY gene HNF1A with an allele frequency of 1.9% in the Greenlandic Inuit and absent elsewhere. Functional assays indicate that it prevents normal splicing of the gene. The variant caused lower 30-min insulin (β = −232 pmol/L, βSD = −0.695, P = 4.43 × 10−4) and higher 30-min glucose (β = 1.20 mmol/L, βSD = 0.441, P = 0.0271) during an oral glucose tolerance test. Furthermore, the variant was associated with type 2 diabetes (OR 4.35, P = 7.24 × 10−6) and HbA1c (β = 0.113 HbA1c%, βSD = 0.205, P = 7.84 × 10−3). The variant explained 2.5% of diabetes variance in Greenland. Interpretation: The reported variant has the largest population impact of any previously reported variant within a MODY gene. Together with the recessive TBC1D4 variant, we show that close to 1 in 5 cases of diabetes (18%) in Greenland are associated with high-impact genetic variants compared to 1–3% in large populations. Funding: Novo Nordisk Foundation, Independent Research Fund Denmark, and Karen Elise Jensen's Foundation.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Altmetric

20.900

0.000