Table 3.

Regions of linkage (multipoint LOD >1.5) to quantitative traits in CARRIAGE Family with citation of studies reporting OA associations that overlap these regions.

OA endophenotype	Chromo- some	Multipoint LOD	Location of peak LOD score in cM	1-LOD interval (cM)	Overlap ping biomarkers	Previously reported OA candidate genes in these region*(cm from peak)	Previous reported OA linkages overlapping these regions
							Phenotype	Peak LOD	Distance (cM)	Population	Ref
PIIANP	6	2.25	50	47–52	HA	HFE(0.1), HLA DR-2/4, TNF(1.3), COL11A2(2.4)	Female Hip	4.8	53–56	UK	(40, 48)
	7	1.97	98	96–102		CD36(5.4)
	8	4.33	8	5–15			Hand JSN	1.57	8.3– 21.3	UK	(13)
	9	1.85	98	72–108		CTSL(9.9), ASPN(2.1) ,OGN(2.2) ,LPAR1(17)	Hand JSN-sum	2.3	76	USA	(11,48,51)
	13	2.35	50	45–57	C2C	LRCH1(0.3)
	15	1.63	9	0–14	COMP
COMP	3	1.61	179	173–183
	5	1.55	127	121–129
	8	3.18	62	60–70			Hand U-Dip	2.56	41.5–79.4	UK	(13)
	8	2.50	149	145–155		WISP1(4.1)					(43)
	14	1.64	40	29–52			Hand U-Dip	1.44	40.5–47.5	UK	(13)
	14	2.57	66	59–82	HA	ESR2(2.2), DIO2(14.7) ,FLRT2(17.7), GPX2(1.7), CALM1(26.5)	Hand U-JSN	2.64	48–57	UK	(13,49,52)
	15	1.60	6	2–20	PIIANP
	16	1.51	50	45–68		IL4R(3.5)	Early-onset Hip	2.6	28–47	Iceland	(53)
							Female Hip	1.7	46	UK	(14)
							Hand U-JSN	2.64	48.5–57.8	UK	(13)
	18	1.82	39	36–49
	18	1.81	72	65–91			Hand OST	1.34	71–85	UK	(13)
							Knee OA	2.41	60.1–86.1	US/UK	(54)
C2C	5	1.98	139	133–144		SLC26A2(14.8)					(55)
	13	1.51	45	41–51	PIIANP	LRCH1(5.3), KL(13.6)	Hand OST	1.28	17.2–25.1	UK	(13)
							Hand K/L sum	1.6	36	USA	(11)
	21	1.52	15	6–22
HA	6	1.69	44	38–48	PIIANP	HLA DR-2/4, HFE(5.9), COL11A2(8.4), TNXB(7.6)	Female Hip	4.8	53–56	UK	(40)
	6	1.96	104	100–108		COL10A1(14.2)	Hand U-OST	1.11	82.6–109.9	Netherlands	(10)
	13	1.83	7	5–11		KL(24.4)
	14	1.57	63	60–67	COMP	ESR2(0.8), GPX2(1.2)	Hand U- JSN	2.64	48–57	UK	(13)

ASPN=asporin;CALM1=calmodulin 1;CD36=platelet glycoprotein 4;COL10A1=collagen, type X, alpha 1;COL11A2=collagen, type XI, alpha ;2CTSL=cathepsin L;DIO2= type II iodothyronine deiodinase;, GPCR,2;ESR2=estrogen receptor 2;FLRT2= fibronectin leucine rich transmembrane protein 2;GPX₂=glutathione peroxidase 2;HLA-DR=human leukocyte antigen of the major histocompatibility complex, MHC class II;HFE=hemochromatosis;IL4R=interleukin 4 receptor; KL=KLOTHO;LPAR1=lysophosphatidic acid receptor 1;LRCH1=leucine-rich repeats and calponin homology domain-containing 1;OGN=osteoglycin;SLC26A2=solute carrier family 26;TNF=tumor necrosis factor;TNXB=tenascin XB;WISP1=wnt-1-induced secreted protein-1. JSN=joint-space narrowing;OST=osteophyte;JSN-sum=sum of joint space narrowing scores;K/L sum=sum of Kellgren-Lawrence scores;U-DIP=unaffected distal interphalangeal;U-JSN=unaffected joint-space narrowing;U-OST=unaffected osteophyte; LOD=Logarithm of odds; h²r=heritability of nearest marker. All candidate genes are less than 10cM from the border of the 1-LOD drop support interval with one exception: the KLOTHO locus is ~31.4 cM from the HA chromosome 13 peak while the 1-LOD interval is 5–11 cM. But this candidate gene has been retained in the gene list because it is <10cM from the 1-LOD drop interval for the C2C chromosome 13 peak (41–51 cM). We defined significant linkage as LOD≥3 and depict these results in bold lettering.