AI Article Synopsis

  • * A study examined genetic sequences from over 3,000 youth-onset T2D patients, finding specific gene variants and associations related to obesity and diabetes.
  • * The research indicates that youth-onset T2D shares genetic factors with adult-onset T2D but shows a higher prevalence of rare variants, suggesting it is a diverse condition that falls between monogenic diabetes and adult-onset T2D.

Article Abstract

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily, producing a growing public health concern that disproportionately affects minority groups. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant (P < 2.6 × 10) gene-level associations (HNF1A, MC4R, ATXN2L). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and β-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies-and rare variants in particular-are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896722PMC
http://dx.doi.org/10.1038/s42255-023-00970-0DOI Listing

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