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. 2019 Jul 25;10:3310. doi: 10.1038/s41467-019-10945-z

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — Modulatory effects of AD-associated haplotypes in APOE and the surrounding region on the expression of nearby genes. a, b Dot plots showing the haplotype–expression association results of the AD-associated haplotypes in PVRL2, APOE, and APOC1 and their nearby genes in (a) blood and (b) the brain. Dot color and size represent effect size and significance level (p or meta-p values), respectively. c Association between PVRL2 beta haplotype with transcript level of blood PVRL2 isoform (ENST00000252485.4) (n = 365, T = −5.470, ***p < 0.001, Beta = −0.449). d Allelic imbalance of PVRL2 variant rs6859 across multiple tissues. One-sample t-test (***p < 0.001). Data were obtained from the GTEx dataset. e Association between PVRL2 minor haplotypes and transcripts of PVRL2 with variant rs6859 in blood (n = 124, T = −3.218, **p < 0.01, Beta = −0.209, for beta haplotype against the major haplotype). f Allelic imbalance of APOE variant rs429358 across multiple tissues. One-sample t-test (***p < 0.001 for representative results). Data were obtained from the GTEx and CommonMind datasets. g PVRL2 haplotype alpha was associated with changes of brain APOE transcript level in individuals not carrying an APOE-ε4 allele (nucleus accumbens, n = 67 or 10 for non-APOE-ε4 carrying individuals harboring 0 or 1 copies of PVRL2 haplotype alpha, respectively; T = 2.963, **p < 0.01, Beta = 0.943, for alpha haplotype against the major haplotype). Data are plotted as mean ± SEM in c, e, and g. Tissue abbreviations: ADRNLG adrenal gland, ARTAORT artery-aorta, ARTCRN artery-coronary, BRNCHA brain-cerebellum, BRNCHB brain-cerebellar hemisphere, BRNCTXA brain-cortex, BRNCTXB brain-frontal cortex (BA9), BRNHPP brain-hippocampus, BRNSPC brain-spinal cord (cervical c-1), HRTAA heart-atrial appendage, HRTLV heart-left ventricle, LIVER liver, LUNG lung, NERVET nerve-tibial, PNCREAS pancreas, SKINNS skin-not sun exposed (Suprapubic), SKINS skin-sun exposed (Lower leg); SPLEEN spleen, STMACH stomach, TESTIS testis, THYROID thyroid, UTERUS uterus, WHLBLD whole blood