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Basic Science and Pathogenesis.

Myriam Fornage1, Rui Xia1, Tamar Sofer2,3

  • 1University of Texas Health Science Center at Houston, Houston, TX, USA.

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Summary
This summary is machine-generated.

Genetic studies on cerebral white matter hyperintensities (WMH) in Hispanic/Latino adults identified known loci and discovered novel ones. This research highlights the importance of diverse populations in understanding WMH genetic architecture.

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Area of Science:

  • Neurogenetics
  • Population Genetics
  • Medical Imaging

Background:

  • Cerebral white matter hyperintensities (WMH) are linked to cognitive decline and dementia.
  • Genetic studies (GWAS) have identified WMH loci, but Hispanic/Latino populations are underrepresented.
  • Hispanic/Latino adults exhibit a higher burden of WMH compared to non-Hispanic white individuals.

Purpose of the Study:

  • To characterize the genetic architecture of WMH in a diverse Hispanic/Latino cohort.
  • To investigate the transferability of known WMH genetic loci.
  • To identify novel WMH loci by leveraging Hispanic/Latino genetic diversity.

Main Methods:

  • Genome-wide association and admixture mapping analyses were performed on 2159 Hispanic/Latino adults.
  • Associations at 27 previously identified WMH loci were investigated.
  • Meta-analysis combined Hispanic/Latino GWAS results with existing GWAS data from other populations.

Main Results:

  • WMH heritability was estimated at 29%.
  • Evidence of transferability was found for 20 out of 27 known WMH loci.
  • A novel locus at 12q22 (rs10859915) and another at 14q13.2 (RALGAPA1) were identified through multi-ancestry meta-analysis and admixture mapping, respectively.

Conclusions:

  • WMH loci identified in other populations are relevant to Hispanic/Latino adults.
  • The diverse Hispanic/Latino population is valuable for fine-mapping known loci and discovering novel ones.
  • This study enhances the understanding of the genetic architecture of cerebral white matter hyperintensities.