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March 29, 2026Alzheimer s & Dementia0 citations

WDR12 and HIVEP3 are contributors to cognitive preservation in Amish SuperAgers

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DDDaniel DorfsmanMPMichael B. ProughAGAlex V. Gulyayev

Key Points

  • The research aims to identify genetic variants associated with cognitive superagers in the Amish population.
  • Grouped 83 Amish superagers into 16 pedigrees for analysis
  • Conducted parametric and non-parametric linkage analysis
  • Assessed variants against Alzheimer's disease and cognitively unimpaired individuals
  • Linked regions identified on chromosomes 1, 2, 7, 16, and 20
  • Strongest association signal observed near the WDR12 locus
  • Eight variants in the HIVEP3 region were significant when comparing superagers to cognitively unimpaired individuals

Abstract

Abstract INTRODUCTION Cognitive SuperAgers (SAs) are individuals aged 80+ with exceptional episodic memory performance for their age, exceeding middle‐aged adult norms. This study integrates family‐ and association‐based methods to identify genetic variants associated with SAs in the Midwestern Amish population. METHODS Eighty‐three Amish SAs were grouped into 16 pedigrees for parametric and non‐parametric linkage analysis. Variants in linked regions (heterogeneity logarithm of the odds HLOD or Kong and Cox logarithm of the odds LOD* ≥ 3) were tested for association with SAs using two contrasts: SA versus Alzheimer's disease (AD; n = 40) and SA versus cognitively unimpaired (CU), age‐matched non‐SA individuals (CU80+; n = 157). RESULTS Evidence of linkage for SAs was observed on chromosomes 1, 2, 7, 16, and 20, with the strongest signal around the AD‐associated locus WDR12 on chromosome 2. Association analysis for SA versus AD identified eight variants in HIVEP3 (chromosome 1) that were nominally significant when comparing SA versus CU80+. DISCUSSION WDR12 and HIVEP3 are potential candidate genes contributing to SAs in the Amish population.

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Cite This Study

Dorfsman et al. (2026) studied this question.

synapsesocial.com/papers/69c8c384de0f0f753b39e55bhttps://doi.org/10.1002/alz.71293
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