Table 4.

Blood DMRs where genetic variation has previously been associated with OFCs

Gene	DMR	Sidak-corrected P value	Findings in this study	N CpGs in DMR	Example of previous findings
TBX1 c	Chr22:19750918-19752870 Chr22:19736256-19736672	1.61 × 10−10 5.03 × 10−4	↑ in CPO vs CLO ↑ in CPO vs CLO	6 2	Variants were associated with non-syndromic CL/P in a candidate gene study of a Brazilian population [41]
COL11A2 c	Chr6:33132086-33132728	2.13 × 10−9	↑ in CPO vs CLO	15	Multiple haplotypes have been associated with non-syndromic CPO compared to unaffected individuals [44]
HOXA2 b	Chr7:27143046-27143807 Chr7:27143235-27143586	1.04 × 10−7 3.9 × 10−2	↑ in CPO vs CLO ↑ in CPO vs CLP	7 7	Hoxa-2 mutant mice have abnormal palatogenesis [71, 72]
CRB2 a	Chr9:126130901-126131310	5.14 × 10−4	↑ in CPO vs CLO	2	Several non-syndromic CL/P susceptibility genes have been identified in the 9q22.32–34.1 region that includes CRB2 [73]
PDGFRA c	Chr4:55090812-55091179	2.71 × 10−2	↑ in CPO vs CLO	2	Mutations in PDGFRA have been associated with non-syndromic CPO [74]
CRISPLD2 c	Chr16:84870066-84870204	3.41 × 10−2	↑ in CPO vs CLO	2	Variants have been associated with non-syndromic CL/P, with some evidence for rs1546124 being associated with CPO in several populations [75]
SMOC1 c	Chr14:70316898-70317240	1.39 × 10−5	↓ in CPO vs CLP	5	A significant proportion of Smoc1 homozygous mutant mice have cleft palate [76]
PVRL1 c	Chr11:119630144-119630363	1.52 × 10−5	↓ in CPO vs CLO	2	Rare and common mutations within PVRL1 were associated with non-syndromic CLP in a family-based study of multiple populations [77]
CCL2 a	Chr17:32582128-32582829	3.00 × 10−4	↓ in CPO vs CLO	6	Variants mapping to CCL2 were associated with non-syndromic CL/P in a candidate gene study [78]

^aIdentified as OFC-related in DisGeNET

^bIdentified as OFC-related in Funato et al.

^cIdentified as OFC-related in both