Genetically-Predicted Adult Height and Alzheimer’s Disease

Abstract

Background:

Observational studies have linked increased adult height with better cognitive performance and reduced risk of Alzheimer’s disease (AD). It is unclear whether the associations are due to shared biological processes that influence height and AD or due to confounding by early life exposures or environmental factors.

Objective:

To use a genetic approach to investigate the association between adult height and AD.

Methods:

We selected 682 single nucleotide polymorphisms (SNPs) associated with height at genome-wide significance (p < 5×10^–8) in the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Summary statistics for each of these SNPs on AD were obtained from the International Genomics of Alzheimer’s Project (IGAP) of 17,008 individuals with AD and 37,154 controls. The estimate of the association between genetically predicted height and AD was calculated using the inverse-variance weighted method.

Results:

The odds ratio of AD was 0.91 (95% confidence interval, 0.86–0.95; p = 9.8×10^–5) per one standard deviation increase (about 6.5 cm) in genetically predicted height based on 682 SNPs, which were clustered in 419 loci. In an analysis restricted to one SNP from each height-associated locus (n = 419 SNPs), the corresponding OR was 0.92 (95% confidence interval, 0.86–0.97; p = 4.8×10^–3).

Conclusions:

This finding suggests that biological processes that influence adult height may have a role in the etiology of AD.