Larsson Susanna C, Traylor Matthew, Burgess Stephen, Markus Hugh S
Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
J Alzheimers Dis. 2017;60(2):691-698. doi: 10.3233/JAD-170528.
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.
To use a genetic approach to investigate the association between adult height and AD.
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.
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).
This finding suggests that biological processes that influence adult height may have a role in the etiology of AD.
观察性研究表明，成人身高增加与更好的认知表现以及降低患阿尔茨海默病（AD）的风险相关。尚不清楚这些关联是由于影响身高和AD的共同生物学过程，还是由于早年暴露或环境因素的混杂作用。
采用遗传学方法研究成人身高与AD之间的关联。
我们在全基因组关联研究（GIANT）联盟中选择了682个与身高相关的单核苷酸多态性（SNP），其全基因组显著性水平为p<5×10-8。这些SNP在阿尔茨海默病国际基因组计划（IGAP）的17008例AD患者和37154例对照中的AD汇总统计数据。使用逆方差加权法计算遗传预测身高与AD之间关联的估计值。
基于682个SNP（分布在419个基因座中），遗传预测身高每增加一个标准差（约6.5厘米），AD的比值比为0.91（95%置信区间，0.86-0.95；p=9.8×10-5）。在仅分析每个与身高相关基因座中的一个SNP（n=419个SNP）的分析中，相应的比值比为0.92（95%置信区间，0.86-0.97；p=4.8×10-3）。
这一发现表明，影响成人身高的生物学过程可能在AD的病因学中起作用。
