TY - JOUR
T1 - Association between alcohol consumption and Alzheimer's disease
T2 - A Mendelian randomization study
AU - Andrews, Shea J.
AU - Goate, Alison
AU - Anstey, Kaarin J.
N1 - Funding Information:
KJA is funded by NHMRC Research Fellowship No. 1002560 . S.J.A. was supported by the ARC Center of Excellence in Population Aging Research , ARC grant CE1101029 , and the JPB Foundation ( http://www.jpbfoundation.org ). AMG was supported by the National Institute on Alcohol Abuse and Alcoholism ( U10AA08401 ) and the JPB Foundation .
Funding Information:
KJA is funded by NHMRC Research Fellowship No. 1002560. S.J.A. was supported by the ARC Center of Excellence in Population Aging Research, ARC grant CE1101029, and the JPB Foundation (http://www.jpbfoundation.org). AMG was supported by the National Institute on Alcohol Abuse and Alcoholism (U10AA08401) and the JPB Foundation. This work was made possible by the generous sharing of GWAS summary statistics. We thank Professor John Chambers for the provision of the summary results data for the GWAS on liver enzyme concentrations in plasma. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i?Select chips were funded by the French National Foundation on Alzheimer's disease and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Universit? de Lille 2, and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant number 503480), Alzheimer's Research UK (Grant number 503176), the Wellcome Trust (Grant n? 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant number 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01?AG?12100, the NHLBI grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association grant ADGC?10?196728. IGAP URL: http://web.pasteur-lille.fr/en/recherche/u744/igap/igap_download.php.
Funding Information:
This work was made possible by the generous sharing of GWAS summary statistics. We thank Professor John Chambers for the provision of the summary results data for the GWAS on liver enzyme concentrations in plasma. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i–Select chips were funded by the French National Foundation on Alzheimer's disease and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm , Institut Pasteur de Lille, Université de Lille 2, and the Lille University Hospital . GERAD was supported by the Medical Research Council (Grant number 503480 ), Alzheimer's Research UK (Grant number 503176 ), the Wellcome Trust (Grant n° 082604/2/07/Z ) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant number 01GI0102 , 01GI0711 , 01GI0420 . CHARGE was partly supported by the NIH / NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01–AG–12100 , the NHLBI grant R01 HL105756 , the Icelandic Heart Association , and the Erasmus Medical Center and Erasmus University . ADGC was supported by the NIH / NIA grants: U01 AG032984 , U24 AG021886 , U01 AG016976 , and the Alzheimer's Association grant ADGC–10–196728 .
Publisher Copyright:
© 2019 the Alzheimer's Association
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Introduction: Observational studies have suggested that light-to-moderate alcohol consumption decreases the risk of Alzheimer's disease, but it is unclear if this association is causal. Methods: Two-sample Mendelian randomization (MR) analysis was used to examine whether alcohol consumption, alcohol dependence, or Alcohol Use Disorder Identification Test (AUDIT) scores were causally associated with the risk of Late-Onset Alzheimer's disease (LOAD) or Alzheimer's disease age of onset survival (AAOS). Additionally, γ-glutamyltransferase levels were included as a positive control. Results: There was no evidence of a causal association between alcohol consumption, alcohol dependence, or AUDIT, and LOAD. Alcohol consumption was associated with an earlier AAOS and increased γ-glutamyltransferase blood concentrations. Alcohol dependence was associated with a delayed AAOS. Discussion: MR found robust evidence of a causal association between alcohol consumption and an earlier AAOS, but not alcohol intake and LOAD risk. The protective effect of alcohol dependence is potentially due to survivor bias.
AB - Introduction: Observational studies have suggested that light-to-moderate alcohol consumption decreases the risk of Alzheimer's disease, but it is unclear if this association is causal. Methods: Two-sample Mendelian randomization (MR) analysis was used to examine whether alcohol consumption, alcohol dependence, or Alcohol Use Disorder Identification Test (AUDIT) scores were causally associated with the risk of Late-Onset Alzheimer's disease (LOAD) or Alzheimer's disease age of onset survival (AAOS). Additionally, γ-glutamyltransferase levels were included as a positive control. Results: There was no evidence of a causal association between alcohol consumption, alcohol dependence, or AUDIT, and LOAD. Alcohol consumption was associated with an earlier AAOS and increased γ-glutamyltransferase blood concentrations. Alcohol dependence was associated with a delayed AAOS. Discussion: MR found robust evidence of a causal association between alcohol consumption and an earlier AAOS, but not alcohol intake and LOAD risk. The protective effect of alcohol dependence is potentially due to survivor bias.
KW - Alcohol consumption
KW - Alcohol dependence
KW - Alzheimer's disease
KW - Mendelian randomization
UR - http://www.scopus.com/inward/record.url?scp=85075820830&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2019.09.086
DO - 10.1016/j.jalz.2019.09.086
M3 - Article
C2 - 31786126
AN - SCOPUS:85075820830
SN - 1552-5260
VL - 16
SP - 345
EP - 353
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 2
ER -