Table 3.

The signals from the Rotterdam genome-wide association scan (GWAS) and from the full arcOGEN GWAS

Study	SNP	Chromosome	P-value	Stratum	Gene	Protein name	Summary of protein function
Rotterdam	rs3815148	7q22	8.0 × 10−8	Knee	PRKAR2B	protein kinase-cAMP-dependent-regulatory-type II-β	Regulator of cAMP signalling
					HPB1	HMG-box transcription factor 1	Transcription factor
					COG5	component of oligomeric golgi complex 5	Golgi morphology and function
					GPR22	G protein-coupled receptor 22	Receptor and membrane protein
					DUS4L	dihydrouridine synthase 4-like	Unknown
					BCAP29	B-cell receptor-associated protein 29	Unknown
arcOGEN	rs6976	3p21.1	7.24 × 10−11	TJR	STAB1	Stabilin-1	Transmembrane receptor
					NT5DC2	5′-nucleotidase domain-containing protein 2	Unknown
					PBRM1	Polybromo-1	Chromatin remodeling and transcriptional activation
					GNL3	Guanine nucleotide-binding protein-like 3	Nuclear protein important for stem cell proliferation
					GLT8D1	Glycosyltransferase 8 domain-containing protein 1	Glycosyltransferase
					SPCS1	Signal peptidase complex subunit 1	Unknown
					NEK4	Serine/threonine-protein kinase Nek4	Kinase
					ITIH1	Inter-alpha-trypsin inhibitor heavy chain H1	Serine protease inhibitor – plasma
					ITIH3	Inter-alpha-trypsin inhibitor heavy chain H3	Serine protease inhibitor – plasma
					ITIH4	Inter-alpha-trypsin inhibitor heavy chain H4	Serine protease inhibitor – plasma
					MUSTN1	Musculoskeletal embryonic nuclear protein 1	Nuclear protein – expressed during skeletogenesis
					TMEM110	Transmembrane protein 110	Unknown
arcOGEN	rs12107036	3q28	6.71 × 10−8	TKR-F	TP63	Tumor protein 63	Transcription factor
arcOGEN	rs10948172	6p21.1	7.92 × 10−8	Male	SUPT3H	Transcription initiation protein SPT3 homologue	Unknown
					RUNX2	Runt-related transcription factor 2	Transcription factor
arcOGEN	rs9350591	6q13-q14.1	2.42 × 10−9	Hip	COL12A1	Collagen α-1(XII) chain	FACIT collagen, interacts with type I collagen
					COX7A2	Cytochrome c oxidase subunit 7A2, mitochondrial	One of the polypeptides of cytochrome C oxidase
					TMEM30A	Cell cycle control protein 50A	Transmembrane protein, transporter
					FILIP1	Filamin-A-interacting protein 1	Interacts with filamin – filamins bind to actin
					SENP6	Sentrin-specific protease 6	Ubiquitin-like molecule ligated to target proteins
					MYO6	Myosin-VI	Intracellular vesicle and organelle transport
					IMPG1	Interphotoreceptor matrix proteoglycan 1	Chondroitin sulfate proteoglycan expressed in the retina
arcOGEN	rs4836732	9q33.1	6.11 × 10−10	THR-F	PAPPA	Pappalysin-1	Secreted metalloproteinase
					ASTN2	Astrotactin-2	Neural migration
					TRIM32	E3 ubiquitin-protein ligase TRIM32	Protein ubiquitination in innate immunity
arcOGEN	rs10492367	12p11.22	1.48 × 10−8	Hip	KLHDC5	Kelch domain-containing protein 5	Protein ubiquitination
					PTHLH	Parathyroid hormone-related protein	Hormone
arcOGEN	rs835487	12q23.3	1.64 × 10−8	THR	CHST11	Carbohydrate sulfotransferase 11	Chondroitin sulfation
arcOGEN	rs8044769	16q12.2	6.85 × 10−8	Female	FTO	α-ketoglutarate-dependent dioxygenase FTO	Unknown

TJR, total joint replacement; TKR-F, total knee replacement in females; THR-F, total hip replacement in females; THR, total hip replacement.