title: Differential parental transmission of markers in RUNX2 among cleft case-parent trios from four populations.
abstract: Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence around 1 in 700 live births. The Runt-related transcription factor 2 (RUNX2) gene has been suggested as a candidate gene for CL/P based largely on mouse models; however, no human studies have focused on RUNX2 as a risk factor for CL/P. This study examines the association between markers in RUNX2 and isolated, nonsyndromic CL/P using a case-parent trio design, while considering parent-of-origin effects. Case-parent trios from four populations (77 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 24 single nucleotide polymorphisms (SNPs) in the RUNX2 gene. We performed the transmission disequilibrium test on individual SNPs. Parent-of-origin effects were assessed using the transmission asymmetry test and the parent-of-origin likelihood ratio test (PO-LRT). When all trios were combined, the transmission asymmetry test revealed a block of 11 SNPs showing excess maternal transmission significant at the P<0.01 level, plus one SNP (rs1934328) showing excess paternal transmission (P=0.002). For the 11 SNPs showing excess maternal transmission, odds ratios of being transmitted to the case from the mother ranged between 3.00 and 4.00. The parent-of-origin likelihood ratio tests for equality of maternal and paternal transmission were significant for three individual SNPs (rs910586, rs2819861, and rs1934328). Thus, RUNX2 appears to influence risk of CL/P through a parent-of-origin effect with excess maternal transmission.
authors: Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
authors: Jae Woong
authors: JW
authors: Sull
authors: Kung-Yee
authors: KY
authors: Liang
authors: Jacqueline B
authors: JB
authors: Hetmanski
authors: Margaret Daniele
authors: MD
authors: Fallin
authors: Roxann G
authors: RG
authors: Ingersoll
authors: Jiwan
authors: J
authors: Park
authors: Yah-Huei
authors: YH
authors: Wu-Chou
authors: Philip K
authors: PK
authors: Chen
authors: Samuel S
authors: SS
authors: Chong
authors: Felicia
authors: F
authors: Cheah
authors: Vincent
authors: V
authors: Yeow
authors: Beyoung Yun
authors: BY
authors: Park
authors: Sun Ha
authors: SH
authors: Jee
authors: Ethylin Wang
authors: EW
authors: Jabs
authors: Richard
authors: R
authors: Redett
authors: Euiju
authors: E
authors: Jung
authors: Ingo
authors: I
authors: Ruczinski
authors: Alan F
authors: AF
authors: Scott
authors: Terri H
authors: TH
authors: Beaty
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D007723:Korea; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008297:Male; D008396:Maryland; D020641:Polymorphism, Single Nucleotide; D012846:Singapore; D013624:Taiwan
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D005819:Genetic Markers; C493709:RUNX2 protein, human