Abstract:
:Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis of toenail Se concentrations, which reflect a longer duration of exposure than blood Se concentrations, including 4162 European descendants from four US cohorts. Toenail Se was measured using neutron activation analysis. We identified a GW-significant locus at 5q14 (P < 1 × 10(-16)), the same locus identified in the published GWAS of blood Se based on independent cohorts. The lead single-nucleotide polymorphism (SNP) explained ∼1% of the variance in toenail Se concentrations. Using GW-summary statistics from both toenail and blood Se, we observed statistical evidence of polygenic overlap (P < 0.001) and meta-analysis of results from studies of either trait (n = 9639) yielded a second GW-significant locus at 21q22.3, harboring CBS (P < 4 × 10(-8)). Proteins encoded by genes at 5q14 and 21q22.3 function in homocysteine (Hcy) metabolism, and index SNPs for each have previously been associated with betaine and Hcy levels in GWAS. Our findings show evidence of a genetic link between Se and Hcy pathways, both involved in cardiometabolic disease.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Cornelis MC,Fornage M,Foy M,Xun P,Gladyshev VN,Morris S,Chasman DI,Hu FB,Rimm EB,Kraft P,Jordan JM,Mozaffarian D,He Kdoi
10.1093/hmg/ddu546subject
Has Abstractpub_date
2015-03-01 00:00:00pages
1469-77issue
5eissn
0964-6906issn
1460-2083pii
ddu546journal_volume
24pub_type
杂志文章,meta分析abstract::DiGeorge syndrome (DGS) is the most common human chromosomal deletion syndrome and is frequently associated with deletions on chromosome 22q11. Approximately 17% of patients with the phenotypic features of this syndrome have no detectable genomic deletion. Animal studies using mouse models have implicated Tbx1 as a cr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi081
更新日期:2005-04-01 00:00:00
abstract::Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused primarily by loss-of-function mutations in NPC1 gene, is characterized neuropathologically by intracellular cholesterol accumulation, gliosis and neuronal loss in selected brain regions. Recent studies have shown that NPC disease exhibits intrig...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds322
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abstract::The identification of mouse models for the various forms of human neurosensory non-syndromic recessive deafness would constitute a major advance in the study of human deafness. Here we describe the localization of a human gene for neurosensory, nonsyndromic recessive deafness (NSRD2) to chromosome 11q13.5 by linkage a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.6.989
更新日期:1994-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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abstract::The von Hippel-Lindau (VHL) tumour suppressorgene product is believed to be involved in the down-regulation of transcriptional elongation by preventing the association of elongin B and C with the catalytic subunit elongin A. Alterations in the human VHL gene lead to VHL disease which is associated with various rare ne...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.2.229
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.6.921
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abstract::Circletail is one of only two mouse mutants that exhibit the most severe form of neural tube defect (NTD), termed craniorachischisis. In this disorder, almost the entire brain and spinal cord is affected, owing to a failure to initiate neural tube closure. Craniorachischisis is a significant cause of lethality in huma...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg014
更新日期:2003-01-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp533
更新日期:2010-02-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.6.711
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.1.27
更新日期:1998-01-01 00:00:00
abstract::DiGeorge syndrome is a human developmental disorder resulting in hypoplasia of the thymus and parathyroids, and conotruncal heart defects. We recently isolated four genes with zinc finger DNA binding motifs mapping to chromosome 22q11.2 DiGeorge critical region. We now report that one of them, ZNF74 gene, is hemizygou...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.10.1583
更新日期:1993-10-01 00:00:00
abstract::A wide spectrum of birth defects are caused by deletions of the DiGeorge syndrome critical region (DGCR) at human chromosome 22q11. Over one hundred such deletions have now been examined and a minimally deleted region of 300kb defined. Within these sequences we have identified a gene expressed during human and murine ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.12.2099
更新日期:1993-12-01 00:00:00
abstract::The chromosome 22q11 region is susceptible to rearrangements that are associated with congenital anomaly disorders and malignant tumors. Three congenital anomaly disorders, cat-eye syndrome, der() syndrome and velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) are associated with tetrasomy, trisomy or monosomy, ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.7.1157
更新日期:1999-07-01 00:00:00
abstract::Migraine is a prevalent, debilitating and costly disorder with an ongoing unmet medical need. Human genetic studies have provided considerable insights into the molecular underpinnings of this complex brain disorder. Classical linkage studies have revealed the causes of familial hemiplegic migraine, while more recentl...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddt364
更新日期:2013-10-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.5.753
更新日期:1997-05-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl135
更新日期:2006-07-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.6.835
更新日期:1996-06-01 00:00:00
abstract::Pathological modifications in the microtubule-associated protein Tau is a common characteristic observed in different neurological diseases, suggesting that analogous metabolic pathways might be similarly affected during neurodegeneration. To identify these molecules and mechanisms, we utilized Drosophila models of hu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu393
更新日期:2014-12-20 00:00:00
abstract::Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neurolig...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa232
更新日期:2021-01-06 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm124
更新日期:2007-07-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.8.1387
更新日期:1994-08-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt518
更新日期:2014-03-01 00:00:00
abstract::Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh035
更新日期:2004-02-01 00:00:00
abstract::The members of the huntingtin-interacting protein-1 (HIP1) family, HIP1 and HIP1-related (HIP1r), are multi-domain proteins that interact with inositol lipids, clathrin and actin. HIP1 is over-expressed in a variety of cancers and both HIP1 and HIP1r prolong the half-life of multiple growth factor receptors. To better...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm076
更新日期:2007-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv336
更新日期:2015-11-01 00:00:00
abstract::Loss of FMR2 causes Fragile X E (FRAXE) site-associated intellectual disability (ID). FMR2 regulates transcription, promotes alternative splicing with preference for G-quartet structure harbouring exons and is localized to the nuclear speckles. In primary skin fibroblasts from FRAXE patients (n = 8), we found a signif...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt155
更新日期:2013-08-01 00:00:00
abstract::Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using ...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
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更新日期:2011-10-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.1.25
更新日期:2001-01-01 00:00:00
abstract::Mutation analysis was performed on DNA samples of 965 individuals from four different ethnic groups in South Africa, in an attempt to determine the spectrum of sequence variants in the haemochromatosis ( HFE ) gene. This population screening approach, utilizing a combined heteroduplex and single-strand conformation po...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.8.1517
更新日期:1999-08-01 00:00:00