当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

Abstract：

:Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10(-8)) level: 14q24.2 (rs227425, P-value 3.98 × 10(-13), SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10(-9), CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Zhang L,Choi HJ,Estrada K,Leo PJ,Li J,Pei YF,Zhang Y,Lin Y,Shen H,Liu YZ,Liu Y,Zhao Y,Zhang JG,Tian Q,Wang YP,Han Y,Ran S,Hai R,Zhu XZ,Wu S,Yan H,Liu X,Yang TL,Guo Y,Zhang F,Guo YF,Chen Y,Chen X,Ta

doi

10.1093/hmg/ddt575

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

1923-33

issue

7

eissn

0964-6906

issn

1460-2083

pii

ddt575

journal_volume

23

pub_type

杂志文章,meta分析

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Knockout of Tmem70 alters biogenesis of ATP synthase and leads to embryonal lethality in mice.

    abstract：:TMEM70, a 21-kDa protein localized in the inner mitochondrial membrane, has been shown to facilitate the biogenesis of mammalian F1Fo ATP synthase. Mutations of the TMEM70 gene represent the most frequent cause of isolated ATP synthase deficiency resulting in a severe mitochondrial disease presenting as neonatal encep...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw295

    authors： Vrbacký M,Kovalčíková J,Chawengsaksophak K,Beck IM,Mráček T,Nůsková H,Sedmera D,Papoušek F,Kolář F,Sobol M,Hozák P,Sedlacek R,Houštěk J

    更新日期：2016-11-01 00:00:00

  • A new model to study neurodegeneration in ataxia oculomotor apraxia type 2.

    abstract：:Ataxia oculomotor apraxia type 2 (AOA2) is a rare autosomal recessive cerebellar ataxia. Recent evidence suggests that the protein defective in this syndrome, senataxin (SETX), functions in RNA processing to protect the integrity of the genome. To date, only patient-derived lymphoblastoid cells, fibroblasts and SETX k...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv296

    authors： Becherel OJ,Sun J,Yeo AJ,Nayler S,Fogel BL,Gao F,Coppola G,Criscuolo C,De Michele G,Wolvetang E,Lavin MF

    更新日期：2015-10-15 00:00:00

  • Reduced cell proliferation and increased apoptosis are significant pathological mechanisms in a murine model of mild pseudoachondroplasia resulting from a mutation in the C-terminal domain of COMP.

    abstract：:Pseudoachondroplasia (PSACH) is one of the more common skeletal dysplasias and results from mutations in cartilage oligomeric matrix protein (COMP). Most COMP mutations identified to date cluster in the TSP3 repeat region of COMP and the mutant protein is retained in the rough endoplasmic reticulum (rER) of chondrocyt...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm155

    authors： Piróg-Garcia KA,Meadows RS,Knowles L,Heinegård D,Thornton DJ,Kadler KE,Boot-Handford RP,Briggs MD

    更新日期：2007-09-01 00:00:00

  • Mutations in the X-linked RP2 gene cause intracellular misrouting and loss of the protein.

    abstract：:Mutations in RP2 cause the second most frequent form of X-linked retinitis pigmentosa, a severe retinal degeneration that leads to loss of visual acuity and blindness. The RP2 gene encodes a protein with homology to cofactor C, a tubulin-folding chaperone. By searching protein sequence databases, we identified a whole...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.11.1177

    authors： Schwahn U,Paland N,Techritz S,Lenzner S,Berger W

    更新日期：2001-05-15 00:00:00

  • Mouse models of X-linked juvenile retinoschisis have an early onset phenotype, the severity of which varies with genotype.

    abstract：:X-linked juvenile retinoschisis (XLRS) is an early-onset inherited condition that affects primarily males and is characterized by cystic lesions of the inner retina, decreased visual acuity and contrast sensitivity and a selective reduction of the electroretinogram (ERG) b-wave. Although XLRS is genetically heterogene...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz122

    authors： Liu Y,Kinoshita J,Ivanova E,Sun D,Li H,Liao T,Cao J,Bell BA,Wang JM,Tang Y,Brydges S,Peachey NS,Sagdullaev BT,Romano C

    更新日期：2019-09-15 00:00:00

  • Evaluating test statistics to select interesting genes in microarray experiments.

    abstract：:A randomization procedure to evaluate the significance level and the false-discovery rate in complex microarray experiments is proposed. A related graph can be used to compare different test statistics that can be used to analyze the same experiment. This graph is closely related to receiver operator characteristic (R...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/11.19.2223

    authors： Kooperberg C,Sipione S,LeBlanc M,Strand AD,Cattaneo E,Olson JM

    更新日期：2002-09-15 00:00:00

  • Ubiquitin-specific protease-14 reduces cellular aggregates and protects against mutant huntingtin-induced cell degeneration: involvement of the proteasome and ER stress-activated kinase IRE1α.

    abstract：:Huntington's disease (HD) is an autosomal inherited neurological disease caused by a CAG-repeat expansion in the first exon of huntingtin gene encoding for the huntingtin protein (Htt). In HD, there is an accumulation of intracellular aggregates of mutant Htt that negatively influence cellular functions. The aggregate...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu317

    authors： Hyrskyluoto A,Bruelle C,Lundh SH,Do HT,Kivinen J,Rappou E,Reijonen S,Waltimo T,Petersén Å,Lindholm D,Korhonen L

    更新日期：2014-11-15 00:00:00

  • CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

    abstract：:Steroid 11 beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol. Severely affected patients carry mutations in the CYB11B1 gene that destroy enzymatic activity. Such patients have signs of androgen excess and usually have hyperten...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/6.11.1829

    authors： Joehrer K,Geley S,Strasser-Wozak EM,Azziz R,Wollmann HA,Schmitt K,Kofler R,White PC

    更新日期：1997-10-01 00:00:00

  • A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27.

    abstract：:Prevalence of coronary heart disease (CHD), of type 2 diabetes (T2DM) and of the metabolic syndrome are in Mauritius amongst the highest in the world. As T2DM and CHD are closely associated and have both a polygenic basis, we conducted a 10 cM genome scan with 403 microsatellite markers in 99 independent families of N...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.24.2751

    authors： Francke S,Manraj M,Lacquemant C,Lecoeur C,Leprêtre F,Passa P,Hebe A,Corset L,Yan SL,Lahmidi S,Jankee S,Gunness TK,Ramjuttun US,Balgobin V,Dina C,Froguel P

    更新日期：2001-11-15 00:00:00

  • A mutational hot spot in keratin 10 (KRT 10) in patients with epidermolytic hyperkeratosis.

    abstract：:Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform erythroderma), is an autosomal dominant human skin disorder. Recently, we and others have described mutations in keratins 1 and 10 (K1 and K10) in patients with this disease. Structure-function models predict that these mutations would impair normal...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.12.2147

    authors： Rothnagel JA,Fisher MP,Axtell SM,Pittelkow MR,Anton-Lamprecht I,Huber M,Hohl D,Roop DR

    更新日期：1993-12-01 00:00:00

  • Human FMRP contains an integral tandem Agenet (Tudor) and KH motif in the amino terminal domain.

    abstract：:Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu586

    authors： Myrick LK,Hashimoto H,Cheng X,Warren ST

    更新日期：2015-03-15 00:00:00

  • Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia.

    abstract：:Mandibuloacral dysplasia (MAD; OMIM 248370) is a rare, genetically and phenotypically heterogeneous, autosomal recessive disorder characterized by skeletal abnormalities including hypoplasia of the mandible and clavicles, acro-osteolysis, cutaneous atrophy and lipodystrophy. A homozygous missense mutation, Arg527His, ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg213

    authors： Agarwal AK,Fryns JP,Auchus RJ,Garg A

    更新日期：2003-08-15 00:00:00

  • Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP.

    abstract：:In mammals, sperm-oocyte fusion initiates Ca(2+) oscillations leading to a series of events called oocyte activation, which is the first stage of embryo development. Ca(2+) signaling is elicited by the delivery of an oocyte-activating factor by the sperm. A sperm-specific phospholipase C (PLCZ1) has emerged as the lik...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv617

    authors： Escoffier J,Lee HC,Yassine S,Zouari R,Martinez G,Karaouzène T,Coutton C,Kherraf ZE,Halouani L,Triki C,Nef S,Thierry-Mieg N,Savinov SN,Fissore R,Ray PF,Arnoult C

    更新日期：2016-03-01 00:00:00

  • Serum calcium and risk of migraine: a Mendelian randomization study.

    abstract：:Migraine affects ∼14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sample Mendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine heada...

    journal_title：Human molecular genetics

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1093/hmg/ddw416

    authors： Yin P,Anttila V,Siewert KM,Palotie A,Davey Smith G,Voight BF

    更新日期：2017-02-15 00:00:00

  • BLM helicase facilitates RNA polymerase I-mediated ribosomal RNA transcription.

    abstract：:Bloom's syndrome (BS) is an autosomal recessive disorder that is invariably characterized by severe growth retardation and cancer predisposition. The Bloom's syndrome helicase (BLM), mutations of which lead to BS, localizes to promyelocytic leukemia protein bodies and to the nucleolus of the cell, the site of RNA poly...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr545

    authors： Grierson PM,Lillard K,Behbehani GK,Combs KA,Bhattacharyya S,Acharya S,Groden J

    更新日期：2012-03-01 00:00:00

  • A window into third-generation sequencing.

    abstract：:First- and second-generation sequencing technologies have led the way in revolutionizing the field of genomics and beyond, motivating an astonishing number of scientific advances, including enabling a more complete understanding of whole genome sequences and the information encoded therein, a more complete characteriz...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddq416

    authors： Schadt EE,Turner S,Kasarskis A

    更新日期：2010-10-15 00:00:00

  • A milieu of regulatory elements in the epidermal differentiation complex syntenic block: implications for atopic dermatitis and psoriasis.

    abstract：:Two common inflammatory skin disorders with impaired barrier, atopic dermatitis (AD) and psoriasis, share distinct genetic linkage to the Epidermal Differentiation Complex (EDC) locus on 1q21. The EDC is comprised of tandemly arrayed gene families encoding proteins involved in skin cell differentiation. Discovery of s...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq019

    authors： de Guzman Strong C,Conlan S,Deming CB,Cheng J,Sears KE,Segre JA

    更新日期：2010-04-15 00:00:00

  • Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy.

    abstract：:Proximal spinal muscular atrophy (SMA) is a common autosomal recessive childhood form of motor neuron disease. Previous studies have highlighted nerve- and muscle-specific events in SMA, including atrophy of muscle fibres and post-synaptic motor endplates, loss of lower motor neuron cell bodies and denervation of neur...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm367

    authors： Murray LM,Comley LH,Thomson D,Parkinson N,Talbot K,Gillingwater TH

    更新日期：2008-04-01 00:00:00

  • A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis.

    abstract：:Epidermolytic hyperkeratosis (EHK) is a blistering skin disease inherited as an autosomal-dominant trait. The disease is caused by genetic defects of the epidermal keratin K1 or K10, leading to an impaired tonofilament network of differentiating epidermal cells. Here, we describe for the first time a kindred with rece...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl028

    authors： Müller FB,Huber M,Kinaciyan T,Hausser I,Schaffrath C,Krieg T,Hohl D,Korge BP,Arin MJ

    更新日期：2006-04-01 00:00:00

  • Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency.

    abstract：:NADH-ubiquinone oxidoreductase (complex I) deficiency is amongst the most encountered defects of the mitochondrial oxidative phosphorylation (OXPHOS) system and is associated with a wide variety of clinical signs and symptoms. Mutations in complex I nuclear structural genes are the most common cause of isolated comple...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh071

    authors： Ugalde C,Janssen RJ,van den Heuvel LP,Smeitink JA,Nijtmans LG

    更新日期：2004-03-15 00:00:00

  • Distortion of allelic expression of apolipoprotein E in Alzheimer's disease.

    abstract：:The APOE epsilon4 allele is a strong genetic susceptibility factor for Alzheimer's disease. Interaction with other biological factors may modulate the effect of the apoE isoforms. However, previous work suggested that other genetic variability within the APOE locus, influencing the effect of the epsilon4 allele, may e...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/6.12.2151

    authors： Lambert JC,Pérez-Tur J,Dupire MJ,Galasko D,Mann D,Amouyel P,Hardy J,Delacourte A,Chartier-Harlin MC

    更新日期：1997-11-01 00:00:00

  • Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis.

    abstract：:Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency results in Lesch-Nyhan disease (LND), where affected individuals exhibit a characteristic neurobehavioral disorder that has been linked with dysfunction of dopaminergic pathways of the basal ganglia. Since the functions of HPRT, a housekeeping enzyme res...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp164

    authors： Ceballos-Picot I,Mockel L,Potier MC,Dauphinot L,Shirley TL,Torero-Ibad R,Fuchs J,Jinnah HA

    更新日期：2009-07-01 00:00:00

  • Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism.

    abstract：:Usher syndrome (USH) is a genetically heterogeneous group of autosomal recessive deaf-blinding disorders. Pathophysiology leading to the blinding retinal degeneration in USH is uncertain. There is evidence for involvement of the photoreceptor cilium, photoreceptor synapse, the adjacent retinal pigment epithelium (RPE)...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddn140

    authors： Jacobson SG,Cideciyan AV,Aleman TS,Sumaroka A,Roman AJ,Gardner LM,Prosser HM,Mishra M,Bech-Hansen NT,Herrera W,Schwartz SB,Liu XZ,Kimberling WJ,Steel KP,Williams DS

    更新日期：2008-08-01 00:00:00

  • Expression of the PTEN tumour suppressor protein during human development.

    abstract：:The tumour suppressor gene PTEN, localized to 10q23.3, is the susceptibility gene for Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba (BRR) syndrome, two hamartoma syndromes with an increased risk of breast and thyroid tumours. Somatic mutations have been found in a variety of human tumours. Functional studies have ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.11.1633

    authors： Gimm O,Attié-Bitach T,Lees JA,Vekemans M,Eng C

    更新日期：2000-07-01 00:00:00

  • Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.

    abstract：:A recurrent t(9;22) (q22;q12) chromosome translocation has been described in extraskeletal myxoid chondrosarcoma (EMC). Fluorescent in situ hybridization experiments performed on one EMC tumour indicated that the chromosome 22 breakpoint occurred in the EWS gene. Northern blot analysis revealed an aberrant EWS transcr...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.12.2219

    authors： Labelle Y,Zucman J,Stenman G,Kindblom LG,Knight J,Turc-Carel C,Dockhorn-Dworniczak B,Mandahl N,Desmaze C,Peter M

    更新日期：1995-12-01 00:00:00

  • Detecting tissue-specific alternative splicing and disease-associated aberrant splicing of the PTCH gene with exon junction microarrays.

    abstract：:Mutations in the human ortholog of Drosophila patched (PTCH) have been identified in patients with autosomal dominant nevoid basal cell carcinoma syndrome (NBCCS), characterized by minor developmental anomalies and an increased incidence of cancers such as medulloblastoma and basal cell carcinoma. We identified many i...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi369

    authors： Nagao K,Togawa N,Fujii K,Uchikawa H,Kohno Y,Yamada M,Miyashita T

    更新日期：2005-11-15 00:00:00

  • Subcellular localization and RNAs determine FUS architecture in different cellular compartments.

    abstract：:Mutations in Fused in sarcoma (FUS) gene cause a subset of familial amyotrophic lateral sclerosis (ALS), a fatal motor neuron degenerative disease. Wild-type FUS is largely localized in the nucleus, but mutant FUS accumulates in the cytoplasm and forms inclusions. It is unclear whether FUS depletion from the nucleus o...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv239

    authors： Yang L,Zhang J,Kamelgarn M,Niu C,Gal J,Gong W,Zhu H

    更新日期：2015-09-15 00:00:00

  • Insulinotropic treatments exacerbate metabolic syndrome in mice lacking MeCP2 function.

    abstract：:Rett syndrome (RTT), an X-linked postnatal disorder, results from mutations in Methyl CpG-binding protein 2 (MECP2). Survival and breathing in Mecp2(NULL/Y) animals are improved by an N-terminal tripeptide of insulin-like growth factor I (IGF-I) treatment. We determined that Mecp2(NULL/Y) animals also have a metabolic...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt111

    authors： Pitcher MR,Ward CS,Arvide EM,Chapleau CA,Pozzo-Miller L,Hoeflich A,Sivaramakrishnan M,Saenger S,Metzger F,Neul JL

    更新日期：2013-07-01 00:00:00

  • Cellular stressors may alter islet hormone cell proportions by moderation of alternative splicing patterns.

    abstract：:Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz094

    authors： Jeffery N,Richardson S,Chambers D,Morgan NG,Harries LW

    更新日期：2019-08-15 00:00:00

  • Chromosome-specific accumulation of aneuploidy in the aging mouse brain.

    abstract：:Chromosomal aneuploidy, the gain or loss of whole chromosomes, is a hallmark of pathological conditions and a causal factor of birth defects and cancer. A number of studies indicate that aneuploid cells are present at a high frequency in the brain of mice and humans, suggesting that mosaic aneuploidies are compatible ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds375

    authors： Faggioli F,Wang T,Vijg J,Montagna C

    更新日期：2012-12-15 00:00:00