A Genome-Wide Association Study of Dementia Using the Electronic Medical Record




Cao, Xiaowen
Dong, Yao
Xing, Li
Zhang, Xuekui

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Dementia is characterized as a decline in cognitive function, including memory, language and problem-solving abilities. In this paper, we conducted a Genome-Wide Association Study (GWAS) using data from the electronic Medical Records and Genomics (eMERGE) network. This study has two aims, (1) to investigate the genetic mechanism of dementia and (2) to discuss multiple p-value thresholds used to address multiple testing issues. Using the genome-wide significant threshold (p ≤ 5 × 10⁻⁸), we identified four SNPs. Controlling the False Positive Rate (FDR) level below 0.05 leads to one extra SNP. Five SNPs that we found are also supported by QQ-plot comparing observed p-values with expected p-values. All these five SNPs belong to the TOMM40 gene on chromosome 19. Other published studies independently validate the relationship between TOMM40 and dementia. Some published studies use a relaxed threshold (p≤1×10⁻⁵) to discover SNPs when the statistical power is insufficient. This relaxed threshold is more powerful but cannot properly control false positives in multiple testing. We identified 13 SNPs using this threshold, which led to the discovery of extra genes (such as ATP10A-DT and PTPRM). Other published studies reported these genes as related to brain development or neuro-development, indicating these genes are potential novel genes for dementia. Those novel potential loci and genes may help identify targets for developing new therapies. However, we suggest using them with caution since they are discovered without proper false positive control.



dementia, GWAS, TOMM40, electronic medical records


Cao, X., Dong, Y., Xing, L., & Zhang, X. (2023). A Genome-Wide Association study of dementia using the Electronic Medical Record. BioMedInformatics, 3(1), 141–149. https://doi.org/10.3390/biomedinformatics3010010