Causal Relationships Between Relative Intake from the Macronutrients and Alzheimer’s Disease: A Two-Sample Mendelian Randomization Study

Article type: Research Article

Authors: Wang, Xiaoxin^{a; 1} | Sun, Hongru^{b; 1} | Pan, Sijia^{a; 1} | Bai, Xiao^{c; 1} | Zhu, Zhuolin^a | Zhang, Runan^a | Li, Chunlong^d | Chen, Yang^a | Bao, Meitong^a | Zhang, Kewei^{e; *} | Feng, Rennan^{a; *}

Affiliations: [a] Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China | [b] Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, P. R. China | [c] Haxi New Area Community Health Service Center, Nangang District, Harbin, Heilongjiang Province, China | [d] Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China | [e] Department of Mathematics, Heilongjiang Institute of Technology, Harbin, China

Correspondence: [*] Corresponding authors: Rennan Feng, PhD, Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, Heilongjiang Province, 150081, China. E-mail: [email protected] and Kewei Zhang, PhD, Department of Mathematics, Heilongjiang Institute of Technology, 999 Hongqi Street, Daowai District, Harbin, Heilongjiang Province, 150050, China. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Some observational studies indicated the associations of relative carbohydrate, sugar, fat, and protein intake and Alzheimer’s disease (AD). But it remains unclear whether the associations are causal. Objective:This study aimed to identify the effects of relative carbohydrate, sugar, fat, and protein intake in the diet on AD. Methods:A two-sample Mendelian randomization was employed. Finally, 14 independent lead SNPs remained in the Social Science Genetic Association Consortium. These SNPs of relative carbohydrate, sugar, fat, and protein intake at the level of genome-wide significance (p < 5×10–8) were used as instrumental variables. The summary data for AD were acquired from the International Genomics of Alzheimer’s Project with a total of 54,162 individuals (17,008 AD patients and 37,154 control participants). Results:This two-sample Mendelian randomization indicated that increased relative protein intake (per 1 standard deviation) causally decreased the AD risk (OR = 0.48, 95% CI: 0.24–0.95, p = 0.036), and increased relative fat intake may decrease the risk of AD (OR = 0.22, 95% CI: 0.06–0.86, p = 0.029). No statistical significance with AD risk was seen for relative carbohydrate or relative sugar intake. Conclusion:A higher relative intake of protein can causally reduce the risk of AD in the elderly. Additionally, a higher relative intake of fat may be protective against AD. No evidence showed that AD was associated with relative carbohydrate and sugar intake.

Keywords: Alzheimer’s disease, dietary carbohydrates, dietary fats, dietary proteins, Mendelian randomization analysis

DOI: 10.3233/JAD-215535

Journal: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 665-673, 2022