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WDR12 and HIVEP3 are contributors to cognitive preservation in Amish SuperAgers
Daniel Dorfsman1,2, Michael B Prough1, Alex Gulyayev1
1John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
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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