<b>The Role of </b><i><b>ONECUT1</b></i><b> Variants in Monogenic and Type 2 Diabetes Mellitus</b>

• DOI: 10.2337/figshare.24018558.v1
• Publication Date: 2023-08-31T11:17:38Z
• Authors: James Russ-Silsby; Kashyap A. Patel; Thomas W. Laver; Gareth Hawkes; Matthew B. Johnson; Matthew N. Wakeling; Prashant P. Patil; Andrew T. Hattersley; Sarah E. Flanagan; Michael N. Weedon; Elisa De Franco

&lt;p dir="ltr"&gt;ONECUT1 (also known as HNF6) is a transcription factor involved in pancreatic development and beta-cell function. Recently, biallelic variants &lt;i&gt;ONECUT1&lt;/i&gt; were reported cause of neonatal diabetes mellitus (NDM) 2 subjects missense monoallelic associated with type possibly maturity-onset the young (MODY). Here we examine role NDM, MODY Type large international cohorts monogenic &gt;400,000 from UK Biobank. We identified frameshift variant NDM one individual. However, found no enrichment or null among 484 individuals clinically suspected MODY, whom all genes had been excluded. Finally, using rare burden test Biobank European cohort, significant association between heterozygous (&lt;i&gt;P=&lt;/i&gt;0.006) but did not find diabetes. Our results confirm &lt;i&gt;ONECUT1 &lt;/i&gt;variants highlight risk for These findings critical &lt;/i&gt;in human function.&lt;/p&gt;