TY - JOUR

T1 - Body mass index and risk of Alzheimer's disease

T2 - A mendelian randomization study of 399,536 individuals

AU - Nordestgaard, Liv Tybjærg

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G.

AU - Frikke-Schmidt, Ruth

PY - 2017/7

Y1 - 2017/7

N2 - Context: Recently, data on 2,000,000 people established that low body mass index (BMI) is associated with increased risk of dementia. Whether this observational association reflects a causal effect remains to be clarified. Objective: Wetested the hypothesis that there is a causal association between low BMI and high risk of Alzheimer's disease. Design, Setting, and Participants: Using a Mendelian randomization approach, we studied 95,578 individuals from the Copenhagen General Population Study (CGPS) with up to 36 years of follow-up and consortia data on 303,958 individuals from the Genetic Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP). Main Outcome Measure: Risk of Alzheimer's disease. Results: The causal odds ratio for a 1-kg/m2 genetically determined lower BMI was 0.98 [95% confidence interval (CI), 0.77 to 1.23] for a weighted allele score in the CGPS. Using 32 BMIdecreasing variants from GIANT and IGAP the causal odds ratio for Alzheimer's disease for a 1-standard deviation (SD) lower genetically determined BMI was 1.02 (95% CI, 0.86 to 1.22). Corresponding observational hazard ratios from the CGPS were 1.07 (95% CI, 1.05 to 1.09) and 1.32 (95% CI, 1.20 to 1.46) for a 1-kg/m2 and a 1-SD lower BMI, respectively. Conclusions: Genetic and hence lifelong low BMI is not associated with increased risk of Alzheimer's disease in the general population. These data suggest that low BMI is not a causal risk factor for Alzheimer's disease and that the corresponding observational association likely is explained by reverse causation or confounding.

AB - Context: Recently, data on 2,000,000 people established that low body mass index (BMI) is associated with increased risk of dementia. Whether this observational association reflects a causal effect remains to be clarified. Objective: Wetested the hypothesis that there is a causal association between low BMI and high risk of Alzheimer's disease. Design, Setting, and Participants: Using a Mendelian randomization approach, we studied 95,578 individuals from the Copenhagen General Population Study (CGPS) with up to 36 years of follow-up and consortia data on 303,958 individuals from the Genetic Investigation of Anthropometric Traits (GIANT) and the International Genomics of Alzheimer's Project (IGAP). Main Outcome Measure: Risk of Alzheimer's disease. Results: The causal odds ratio for a 1-kg/m2 genetically determined lower BMI was 0.98 [95% confidence interval (CI), 0.77 to 1.23] for a weighted allele score in the CGPS. Using 32 BMIdecreasing variants from GIANT and IGAP the causal odds ratio for Alzheimer's disease for a 1-standard deviation (SD) lower genetically determined BMI was 1.02 (95% CI, 0.86 to 1.22). Corresponding observational hazard ratios from the CGPS were 1.07 (95% CI, 1.05 to 1.09) and 1.32 (95% CI, 1.20 to 1.46) for a 1-kg/m2 and a 1-SD lower BMI, respectively. Conclusions: Genetic and hence lifelong low BMI is not associated with increased risk of Alzheimer's disease in the general population. These data suggest that low BMI is not a causal risk factor for Alzheimer's disease and that the corresponding observational association likely is explained by reverse causation or confounding.

U2 - 10.1210/jc.2017-00195

DO - 10.1210/jc.2017-00195

M3 - Journal article

C2 - 28609829

AN - SCOPUS:85023201304

VL - 102

SP - 2310

EP - 2320

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -