Whole genome pleiotropy between Alzheimer’s Disease and Autoimmune Disorders — The Association Specialists
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Whole genome pleiotropy between Alzheimer’s Disease and Autoimmune Disorders (21806)

Sarah K Davies 1 2 , Nesli Avgan 1 2 , Cue H Lee 3 4 , Bryce Vissel 1 2
  1. St Vincents Centre for Applied Medical Research, Sydney, NSW, Australia
  2. Centre for Neuroscience and Regenerative Medicine, Revesby, NSW, Australia
  3. Department for Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, Jongno District, South Korea
  4. Department of convergence Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, South Korea

We aimed to determine pleiotropic risk genes mediating Alzheimer's (AD) and 7 autoimmune diseases using next generation multi-trait analysis tool, PLEIO. 

We analysed the largest and most recent GWAS from AD in combination with 7 autoimmune diseases including Inflammatory Bowel Disease (IBD), Crohn's Disease (CD), Ulcerative Colitis (UC), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Type 1 Diabetes (T1D) and Vitiligo (Vi). We used the novel tool PLEIO to evaluate the influence of AD risk mutations in a multi-trait analysis of well-established autoimmune diseases. Unlike traditional meta analysis, PLEIO factors in the complex genetic architecture of traits such as correlations and heritabilities, and utilises a joint likelihood framework to increase power to detect pleiotropic single nucleotide polymorphisms (SNPs). 

Autoimmune disease showed a higher percentage SNP heritability (H2 = 0.14 - 0.4) compared to AD (H2 = 0.07). Genetically, AD was positively correlated with CD, IBD, SLE, UC and Vi (rg = 0.002 - 0.01) and negatively correlated with RA and T1D (rg =-0.09 - -0.1). Pleiotropic analysis of disease associated loci for AD and 7 autoimmune diseases uncovered 40 novel SNPs, 29 of which are located on protein coding regions. Functional annotation identified 7 SNPs as expression quantitative trait loci (eQTLs) significantly associated with changes of expression for 10 genes. Gene prioritisation analysis identified 9 of the 10 genes as likely causal for disease outcomes. 

Our study presents the largest pleiotropy study investigating the shared genetic etiology of AD and autoimmune disease with a newly developed analysis method.