Arid
DOI10.1093/hmg/ddv210
A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius
Chesi, Alessandra1; Mitchell, Jonathan A.5; Kalkwarf, Heidi J.7; Bradfield, Jonathan P.2; Lappe, Joan M.8; McCormack, Shana E.1,3,6; Gilsanz, Vicente9; Oberfield, Sharon E.10; Hakonarson, Hakon1,2,6; Shepherd, John A.11; Kelly, Andrea4,6; Zemel, Babette S.4,6; Grant, Struan F. A.1,2,3,6
通讯作者Chesi, Alessandra
来源期刊HUMAN MOLECULAR GENETICS
ISSN0964-6906
EISSN1460-2083
出版年2015
卷号24期号:17页码:5053-5059
英文摘要

Childhood fractures are common, with the forearm being the most common site. Genome-wide association studies (GWAS) have identified more than 60 loci associated with bone mineral density (BMD) in adults but less is known about genetic influences specific to bone in childhood. To identify novel genetic factors that influence pediatric bone strength at a common site for childhood fractures, we performed a sex-stratified trans-ethnic genome-wide association study of areal BMD(aBMD) and bone mineral content (BMC) Z-scores measured by dual energy X-ray absorptiometry at the one-third distal radius, in a cohort of 1399 children without clinical abnormalities in bone health. We tested signals with P < 5 x 10(-6) for replication in an independent, same-age cohort of 486 Caucasian children. Two loci yielded a genome-wide significant combined P-value: rs7797976 within CPED1 in females [P = 2.4 x 10(-11), beta = -0.30 standard deviations (SD) per T allele; aBMD-Z] and rs7035284 at 9p21.3 in males (P = 1.2 x 10(-8), beta = 0.28 SD per G allele; BMC-Z). Signals at the CPED1-WNT16-FAM3C locus have been previously associated with BMD at other skeletal sites in adults and children. Our result at the distal radius underscores the importance of this locus at multiple skeletal sites. The 9p21.3 locus is within a gene desert, with the nearest gene flanking each side being MIR31HG and MTAP, neither of which has been implicated in BMD or BMC previously. These findings suggest that genetic determinants of childhood bone accretion at the radius, a skeletal site that is primarily cortical bone, exist and also differ by sex.


类型Article
语种英语
国家USA
收录类别SCI-E
WOS记录号WOS:000361316300021
WOS关键词BONE-MINERAL DENSITY ; FRACTURES ; CHILDREN ; SITES ; WOMEN ; RISK ; MASS ; SEX ; HIP ; AGE
WOS类目Biochemistry & Molecular Biology ; Genetics & Heredity
WOS研究方向Biochemistry & Molecular Biology ; Genetics & Heredity
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/187687
作者单位1.Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA;
2.Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA;
3.Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA;
4.Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA;
5.Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA;
6.Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA;
7.Cincinnati Childrens Hosp Med Ctr, Div Gen & Community Pediat, Cincinnati, OH 45229 USA;
8.Creighton Univ, Dept Med, Div Endocrinol, Omaha, NE 68178 USA;
9.Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA;
10.Columbia Univ Med Ctr, Dept Pediat, Div Pediat Endocrinol Diabet & Metab, New York, NY USA;
11.Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA
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Chesi, Alessandra,Mitchell, Jonathan A.,Kalkwarf, Heidi J.,et al. A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius[J],2015,24(17):5053-5059.
APA Chesi, Alessandra.,Mitchell, Jonathan A..,Kalkwarf, Heidi J..,Bradfield, Jonathan P..,Lappe, Joan M..,...&Grant, Struan F. A..(2015).A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius.HUMAN MOLECULAR GENETICS,24(17),5053-5059.
MLA Chesi, Alessandra,et al."A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius".HUMAN MOLECULAR GENETICS 24.17(2015):5053-5059.
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