Excess of Rare Coding Variants in PLD3 in Late- but Not Early-Onset Alzheimer S Disease

SUPPLEMENTARY INFORMATION

Excess of rare coding variants in PLD3 in late- but not early-onset Alzheimer`s disease

Eva C. Schulte,1,2 Alexander Kurz3, Panagiotis Alexopoulos3, Harald Hampel4,5, Annette Peters6, Christian Gieger7, Dan Rujescu8, Janine Diehl-Schmid3, Juliane Winkelmann1,2,9,10,11*

1Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany 2Institut für Humangenetik, Helmholtz Zentrum München, 85764 Neuherberg, Germany 3Klinik und Poliklinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany 4AXA Research Fund & UPMC Chair 5Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France 6Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany 7Institute of Genetic Epidemiology, Helmholtz Zentrum München, 85764 Neuherberg, Germany 8Klinik für Psychiatrie, Universität Halle, Halle, Germany 9Institut für Humangenetik, Technische Universität München, 81675 Munich, Germany 10Munich Cluster for Systems Neurology (SyNergy), Munich, Germany 11Department of Neurology and Neurosciences, Stanford University, Palo Alto, CA, 94304, USA

*address correspondence to: Juliane Winkelmann Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München Ismaningerstr. 22, 81675 Munich, Germany Phone: +49 89 4140 4688 Fax: +49 89 4140 4867 Email: [email protected], [email protected] SUPPLEMENTARY TABLES

TABLE S1

LOAD EOAD all AD FTLD KORA controls (n=960) (n=139) (n=1089) (n=138) (n=1456) non-syn 10 3 13 1 19 syn 50 5 55 4 44 nearsplice 2 0 2 0 2 total 62 8 70 5 65

Variant count for different classes of variants in the different study samples. AD=Alzheimer`s disease; LOAD=late onset AD; EOAD=early onset AD; FTLD=frontotemporolobar degeneration; non-syn=non-synonymous; syn=synonymous

TABLE S2

MAF (%) LOAD EOAD LOAD+EOAD FTLD KORA controls non-syn 0.005 0.011 0.006 0.004 0.007 syn 0.026 0.018 0.025 0.014 0.015 nearsplice 0.001 0.000 0.001 0.000 0.001 total 0.032 0.029 0.032 0.018 0.022

Distribution of minor allele frequencies (MAFs) for different classes of identified variants in the different sample groups.

TABLE S3

Burden-test p-values vs. KORA controls (χ2 test) LOAD EOAD LOAD+EOAD FTLD non-syn 0.562 0.411 0.803 0.559 syn 0.007 0.709 0.009 0.938 nearsplice 0.674 0.662 0.770 0.662 total 0.034 0.541 0.031 0.648 P-values vs. KORA general population controls for χ2-based burden testing of variants in PLD3. Gray shading indicates significant results.

TABLE S4

Burden-test ORs vs. KORA controls (χ2 test) LOAD EOAD LOAD+EOAD FTLD non-syn 0.79 (0.36-1.71) 1.66 (0.48-5.70) 0.91 (0.44-1.85) 0.55 (0.07-4.15) syn 1.74 (1.15-2.62) 1.17 (0.45-2.99) 1.68 (1.13-2.52) 0.93 (0.33-2.64) nearsplice 1.51 (0.21-10.79) 2.08 (0.09-43.65) 1.33 (0.18-9.51) 2.10 (0.10-43.97) total 1.46 (1.02-2.07) 1.28 (0.60-2.73) 1.45 (1.03-2.05) 0.79 (0.31-1.99)

Odds ratios (OR) and 95% confidence interval vs. KORA general population controls for χ2-based burden testing of variants in PLD3. Gray shading indicates significant results.