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The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.

ABSTRACT: Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort.Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score.Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.

SUBMITTER: Zhao J

PROVIDER: S-EPMC2894790 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.

Zhao Jianhua J Li Mingyao M Bradfield Jonathan P JP Zhang Haitao H Mentch Frank D FD Wang Kai K Sleiman Patrick M PM Kim Cecilia E CE Glessner Joseph T JT Hou Cuiping C Keating Brendan J BJ Thomas Kelly A KA Garris Maria L ML Deliard Sandra S Frackelton Edward C EC Otieno F George FG Chiavacci Rosetta M RM Berkowitz Robert I RI Hakonarson Hakon H Grant Struan F A SF

BMC medical genetics 20100614

<h4>Background</h4>Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.<h4>Methods</h4>To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for h ...[more]

PMID: 20546612

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Project description:ObjectiveTo explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci.MethodsA questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke.ResultsA total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033).ConclusionDecreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.

Project description:BackgroundAsthma exacerbations are a major cause of morbidity and medical cost.ObjectiveThe objective of this study was to identify genetic predictors of exacerbations in asthmatic subjects.MethodsWe performed a genome-wide association study meta-analysis of acute asthma exacerbation in 2 pediatric clinical trials: the Childhood Asthma Management Program (n = 581) and the Childhood Asthma Research and Education (n = 205) network. Acute asthma exacerbations were defined as treatment with a 5-day course of oral steroids. We obtained a replication cohort from Biobank of Vanderbilt University Medical Center (BioVU; n = 786), the Vanderbilt University electronic medical record-linked DNA biobank. We used CD4(+) lymphocyte genome-wide mRNA expression profiling to identify associations of top single nucleotide polymorphisms with mRNA abundance of nearby genes.ResultsA locus in catenin (cadherin-associated protein), alpha 3 (CTNNA3), reached genome-wide significance (rs7915695, P = 2.19 × 10(-8); mean exacerbations, 6.05 for minor alleles vs 3.71 for homozygous major alleles). Among the 4 top single nucleotide polymorphisms replicated in BioVU, rs993312 in Sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3D (SEMA3D) was significant (P = .0083) and displayed stronger association among African Americans (P = .0004 in BioVU [mean exacerbations, 3.91 vs 1.53]; P = .0089 in the Childhood Asthma Management Program [mean exacerbations, 6.0 vs 3.25]). CTNNA3 variants did not replicate in BioVU. A regulatory variant in the CTNNA3 locus was associated with CTNNA3 mRNA expression in CD4(+) cells from asthmatic patients (P = .00079). CTNNA3 appears to be active in the immune response, and SEMA3D has a plausible role in airway remodeling. We also provide a replication of a previous association of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7), with asthma exacerbation.ConclusionsWe identified 2 loci associated with exacerbations through a genome-wide association study. CTNNA3 met genome-wide significance thresholds, and SEMA3D replicated in a clinical biobank database.

Dataset Information

The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.

Publications

The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.

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