Association of type 2 diabetes GWAS loci and the risk of Parkinson's and Alzheimer's diseases.
BACKGROUND
Insulin and insulin-like growth factor contribute to normal brain function. Recent experimental and clinical studies showed that type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD) or Alzheimer's disease (AD) share several dysregulated pathways.


OBJECTIVE
We aimed to investigate whether genome-wide significant loci of T2DM are associated with the risk of PD and AD as well as the severity of cognitive impairment.


METHODS
Study subjects were 500 PD patients, 400 AD patients, and 500 unrelated controls. We selected 32 genetic variants from 11 genes (CDC123, CDKAL1, CDKN2B, FTO, GLIS3, HHEX, IGF2BP2, KCNJ11, KCNQ1, SLC30A8, and TCF7L2) and intergenic regions based on results of recent genome-wide association studies (GWAS) in T2DM. These variants were reported to be T2DM-susceptibility loci and have been replicated in other independent studies. All association analyses were performed using logistic regression models, adjusting for age and sex.


RESULTS
KCNQ1 SNP rs163182 showed the strongest association with AD, but it was not significant after Bonferroni correction (OR = 1.30, 95% CI = 1.07-1.59, Pcorrected = 0.32). In PD patients, CDC123 SNP rs11257655 showed modest association with MMSE score <26, and CDKN2B SNPs (rs2383208, rs10965250, and rs10811661) showed modest association with MoCA score <26, which were not significant after Bonferroni correction. Other genetic variants had no association with the risk of PD or AD and the severity of cognitive impairment.


CONCLUSIONS
Our results suggest that genome-wide significant loci of T2DM play no major role in the risk and cognitive impairment of PD and AD.
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: sjchung@amc.seoul.kr.
Sun Ju
SJ
Chung
Department of Neurology, Bobath Memorial Hospital, Seongnam, Republic of Korea.
Mi-Jung
MJ
Kim
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Juyeon
J
Kim
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Ho-Sung
HS
Ryu
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Young Jin
YJ
Kim
Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Seong Yoon
SY
Kim
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Jae-Hong
JH
Lee
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics / Q000523:psychology; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics / Q000523:psychology; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea / Q000453:epidemiology; D012306:Risk
Alzheimer's disease; Genetic variation; Genome; Parkinson's disease; Type 2 diabetes mellitus