Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis

被引：29

作者：

Feenstra, Bjarke ^{[1
]}

Geller, Frank ^{[1
]}

Krogh, Camilla ^{[1
]}

Hollegaard, Mads V. ^{[2
]}

Gortz, Sanne ^{[1
]}

Boyd, Heather A. ^{[1
]}

Murray, Jeffrey C. ^{[3
]}

Hougaard, David M. ^{[2
]}

Melbye, Mads ^{[1
]}

机构：

[1] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[2] Statens Serum Inst, Sect Neonatal Screening & Hormones, DK-2300 Copenhagen, Denmark

[3] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 03期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; HERITABILITY; INHERITANCE;

D O I：

10.1038/ng.1067

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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 x 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 x 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 x 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.

引用

页码：334 / U1601

页数：5

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