Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
Infantile hypertrophic pyloric stenosis (IHPS) is a severe condition characterized by hypertrophy of the pyloric sphincter muscle. We conducted a genome-wide association study (GWAS) on 1,001 surgery-confirmed cases and 2,401 controls from Denmark. The six most strongly associated loci were tested in a replication set of 796 cases and 876 controls. Three SNPs reached genome-wide significance. One of these SNPs, rs11712066 (odds ratio (OR) = 1.61; P = 1.5 × 10(-17)) at 3p25.1, is located 150 kb upstream of MBNL1, which encodes a factor that regulates splicing transitions occurring shortly after birth. The second SNP, rs573872 (OR = 1.41; P = 4.3 × 10(-12)), maps to an intergenic region at 3p25.2 approximately 1.3 Mb downstream of MBNL1. The third SNP, rs29784 (OR = 1.42; P = 1.5 × 10(-15)) at 5q35.2, is 64 kb downstream of NKX2-5, which is involved in development of cardiac muscle tissue and embryonic gut development.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. fee@ssi.dk
Bjarke
B
Feenstra
Frank
F
Geller
Camilla
C
Krogh
Mads V
MV
Hollegaard
Sanne
S
Gørtz
Heather A
HA
Boyd
Jeffrey C
JC
Murray
David M
DM
Hougaard
Mads
M
Melbye
D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003718:Denmark; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D046248:Pyloric Stenosis, Hypertrophic / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C493663:MBNL1 protein, human; C095552:NKX2-5 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors