WDR12 and HIVEP3 are contributors to cognitive preservation in Amish SuperAgers.

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.