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. 2021 Dec 2;11:23314. doi: 10.1038/s41598-021-98792-1

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© The Author(s) 2021

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Most significant pathways identified by functional GWAS. (A) cholinergic synapse pathway and (B) calcium signalling pathway. The two KEGG pathways are interconnected (B). The KEGG pathway calcium signalling has been edited to add three additional genes of relevance (green rectangles). Each node can represent multiple genes. Symbols in the two panels are the same as in the original KEGG pathway map (NCX: Na/Ca exchanger; PMCA: ATPase plasma membrane Ca2 + transporting; CaV12: calcium voltage-gated channel subunit alpha1 A and C; ROC: nicotinic acetylcholine receptor alpha-7; GPCR: cysteinyl leukotriene receptor 1; PTK: epidermal growth factor receptor; CD38: ADP-ribosyl cyclase 1; PLC: phosphatidylinositol phospholipase C; Gs: guanine nucleotide-binding protein G(s) subunit alpha; Gq: guanine nucleotide-binding protein subunit alpha-11; SERCA: P-type Ca2 + transporter type 2A; IP3R: inositol 1,4,5-triphosphate receptor type 1; TnC: troponin C; MLCK: myosin-light-chain kinase; PHK: phosphorylase kinase alpha/beta subunit; NOS: nitric-oxide synthase; PDE1: calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase; FAK2: focal adhesion kinase 2; IP3 3 K: 1D-myo-inositol-triphosphate 3-kinase; M1: muscarinic acetylcholine receptor M1; M2: muscarinic acetylcholine receptor M2; M3: muscarinic acetylcholine receptor M3; M5: muscarinic acetylcholine receptor M5; VGCC: calcium voltage-gated channel subunit alpha1 C; AChE: acetylcholinesterase; Gi/o: G protein subunit beta 5; CAMK: CAMK2G and CAMK2B; CREB: cAMP responsive element binding protein 3; PKB/Akt: AKT serine/threonine kinase 3). Genes shown in this figure map to SNPs with p value < 0.05.