WDR12 and HIVEP3 are Contributors to Cognitive Preservation in Amish SuperAgers
Dorfsman, D. A.; Prough, M. B.; Gulyayev, A.; Caywood, L. J.; Clouse, J. E.; Herington, S. D.; Slifer, S. H.; Adams, L. D.; Laux, R. A.; Song, Y. E.; Lynn, A.; Fuzzell, S. L.; Hochstetler, S. D.; Miskimen, K.; Main, L. R.; Wang, P.; Liu, Y.; Moore, N.; Ogrocki, P.; Lerner, A. J.; Vance, J. M.; Cuccaro, M. L.; Haines, J. L.; Pericak-Vance, M. A.; Scott, W. K.
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INTRODUCTIONCognitive SuperAgers (SA) 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 SA in the Midwestern Amish population. METHODS83 Amish SA were grouped into 16 pedigrees for parametric and non-parametric linkage analysis. Variants in linked regions (HLOD/LOD*[≥]3) were tested for association with SA using two contrasts: SA vs. Alzheimers disease (AD; n=40), and SA vs. cognitively unimpaired (CU), age-matched non-SA individuals (CU80+; n=157). RESULTSEvidence of linkage for SA 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 vs. AD identified eight variants in HIVEP3 (chromosome 1) that were nominally significant when comparing SA vs. CU80+. DISCUSSIONWDR12 and HIVEP3 are potential candidate genes contributing to SA in the Amish population.
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