Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
WDR12 and HIVEP3 are contributors to cognitive preservation in Amish SuperAgers.
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Dorfsman Daniel, Prough Michael B, Gulyayev Alex, Caywood Laura J, Clouse Jason E, Herington Sharlene D, Slifer Susan H, Adams Larry D, Laux Renee A, Song Yeunjoo E, Lynn Audrey, Fuzzell Sarada L, Hochstetler Sherri D, Miskimen Kristy, Main Leighanne R, Wang Ping, Liu Yining, Moore Noel, Ogrocki Paula, Lerner Alan J, Vance Jeffery M, Cuccaro Michael L, Haines Jonathan L, Pericak-Vance Margaret A, Scott William K
Аннотация
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.
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.