当前位置： SCI文献检索 > AMERICAN JOURNAL OF HUMAN GENETICS期刊下所有文献 > Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

Abstract：

:To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Saxena R,Elbers CC,Guo Y,Peter I,Gaunt TR,Mega JL,Lanktree MB,Tare A,Castillo BA,Li YR,Johnson T,Bruinenberg M,Gilbert-Diamond D,Rajagopalan R,Voight BF,Balasubramanyam A,Barnard J,Bauer F,Baumert J,Bhangale T,Böh

doi

10.1016/j.ajhg.2011.12.022

subject

Has Abstract

pub_date

2012-03-09 00:00:00

pages

410-25

issue

3

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(12)00031-6

journal_volume

90

pub_type

杂志文章,meta分析

相关文献

AMERICAN JOURNAL OF HUMAN GENETICS文献大全
  • Homozygosity mapping in families with Joubert syndrome identifies a locus on chromosome 9q34.3 and evidence for genetic heterogeneity.

    abstract：:Joubert syndrome is a rare developmental defect of the cerebellar vermis, with autosomal recessive inheritance. The phenotype is highly variable and may include episodic hyperpnea, abnormal eye movements, hypotonia, ataxia, developmental delay, and mental retardation. Even within sibships the phenotype may vary, makin...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302655

    authors： Saar K,Al-Gazali L,Sztriha L,Rueschendorf F,Nur-E-Kamal M,Reis A,Bayoumi R

    更新日期：1999-12-01 00:00:00

  • Mapping of Alport syndrome to the long arm of the X chromosome.

    abstract：:Five X-chromosome DNA markers were typed on 261 members of three large kindreds with Alport syndrome (hereditary glomerulonephritis). Lod scores greater than 3.0 for linkage between the disease locus and two of the markers confirmed X-linked inheritance of the disease. A decreasing gradient in the estimated recombinat...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Atkin CL,Hasstedt SJ,Menlove L,Cannon L,Kirschner N,Schwartz C,Nguyen K,Skolnick M

    更新日期：1988-02-01 00:00:00

  • HLA antigens in cardiomyopathic Chilean chagasics.

    abstract：:The distribution of HLA antigens in a sample of 124 Chagas serologically positive Chilean individuals was studied. The sample was subdivided according to the presence or absence of chagasic cardiomyopathy, in order to search for genetic differences associated with this pathological condition. The frequency of antigen ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Llop E,Rothhammer F,Acuña M,Apt W

    更新日期：1988-11-01 00:00:00

  • Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region.

    abstract：:Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encodin...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/514843

    authors： Arngrímsson R,Hayward C,Nadaud S,Baldursdóttir A,Walker JJ,Liston WA,Bjarnadóttir RI,Brock DJ,Geirsson RT,Connor JM,Soubrier F

    更新日期：1997-08-01 00:00:00

  • Genetic determination of high-density lipoprotein-cholesterol and apolipoprotein A-1 plasma levels in a family study of cardiac catheterization patients.

    abstract：:Plasma levels of two lipoprotein risk factors, high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-1 (apo A-1), have been shown to be negatively associated with the risk of developing coronary artery disease, and several reports have examined familial factors in HDL-C and apo A-1 levels. A number of stud...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Prenger VL,Beaty TH,Kwiterovich PO

    更新日期：1992-11-01 00:00:00

  • Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

    abstract：:Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2011.10.002

    authors： Bown MJ,Jones GT,Harrison SC,Wright BJ,Bumpstead S,Baas AF,Gretarsdottir S,Badger SA,Bradley DT,Burnand K,Child AH,Clough RE,Cockerill G,Hafez H,Scott DJ,Futers S,Johnson A,Sohrabi S,Smith A,Thompson MM,van Bockxm

    更新日期：2011-11-11 00:00:00

  • So many Nigerians: why is Nigeria overrepresented as the ancestral genetic homeland of Legacy African North Americans?

    abstract：:The genetics of African North Americans are complex amalgamations of various West and Central African peoples with modest gene flow from specific European and Amerindian peoples. A comprehensive understanding of African North American biohistory is a prerequisite for accurate interpretations of the ancestral genetics ...

    journal_title：American journal of human genetics

    pub_type： 评论,杂志文章

    doi：10.1016/j.ajhg.2020.10.010

    authors： Jackson FLC

    更新日期：2021-01-07 00:00:00

  • Hereditary multiple exostoses (EXT): mutational studies of familial EXT1 cases and EXT-associated malignancies.

    abstract：:Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, loca...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Hecht JT,Hogue D,Wang Y,Blanton SH,Wagner M,Strong LC,Raskind W,Hansen MF,Wells D

    更新日期：1997-01-01 00:00:00

  • "Cryptic" repeating triplets of purines and pyrimidines (cRRY(i)) are frequent and polymorphic: analysis of coding cRRY(i) in the proopiomelanocortin (POMC) and TATA-binding protein (TBP) genes.

    abstract：:Triplets of the form of purine, purine, pyrimidine (RRY(i)) are enhanced in frequency in the genomes of primates, rodents, and bacteria. Some RRY(i) are "cryptic" repeats (cRRY(i)) in which no one tandem run of a trinucleotide predominates. A search of human GenBank sequence revealed that the sequences of cRRY(i) are ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Gostout B,Liu Q,Sommer SS

    更新日期：1993-06-01 00:00:00

  • In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome.

    abstract：:Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2012.10.002

    authors： Carmignac V,Thevenon J,Adès L,Callewaert B,Julia S,Thauvin-Robinet C,Gueneau L,Courcet JB,Lopez E,Holman K,Renard M,Plauchu H,Plessis G,De Backer J,Child A,Arno G,Duplomb L,Callier P,Aral B,Vabres P,Gigot N,Arbu

    更新日期：2012-11-02 00:00:00

  • A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa.

    abstract：:Autosomal dominant retinitis pigmentosa (ADRP) has recently been linked to locus D3S47 (probe C17), with no recombination, in a single large Irish family. Other ADRP pedigrees have shown linkage at zero recombination, linkage with recombination, and no linkage, demonstrating genetic heterogeneity. The gene encoding rh...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Inglehearn CF,Bashir R,Lester DH,Jay M,Bird AC,Bhattacharya SS

    更新日期：1991-01-01 00:00:00

  • HLA-DQ primarily confers protection and HLA-DR susceptibility in type I (insulin-dependent) diabetes studied in population-based affected families and controls.

    abstract：:The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM. HLA haplotype...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Kockum I,Wassmuth R,Holmberg E,Michelsen B,Lernmark A

    更新日期：1993-07-01 00:00:00

  • Comparative linkage-disequilibrium analysis of the beta-globin hotspot in primates.

    abstract：:Recombination rates vary both across the genome and between different species, but little information is available about the temporal and physical scales over which such rates change. To shed light on these questions, we performed a high-resolution analysis of a genomic region within the beta-globin gene cluster that ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/380311

    authors： Wall JD,Frisse LA,Hudson RR,Di Rienzo A

    更新日期：2003-12-01 00:00:00

  • Chromosomal localization of a human band 3-like gene to region 7q35----7q36.

    abstract：:Band 3, the major transmembrane protein of erythrocytes, mediates the exchange of anions across the membrane and anchors the erythroid membrane skeleton. Proteins immunologically related to Band 3 have been detected in a variety of nonerythroid cells. We have isolated a human cDNA clone that encodes a protein related ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Palumbo AP,Isobe M,Huebner K,Shane S,Rovera G,Demuth D,Curtis PJ,Ballantine M,Croce CM,Showe LC

    更新日期：1986-09-01 00:00:00

  • Genetic counseling in rare syndromes: a resampling method for determining an approximate confidence interval for gene location with linkage data from a single pedigree.

    abstract：:Multipoint linkage analysis is a powerful method for mapping a rare disease gene on the human gene map despite limited genotype and pedigree data. However, there is no standard procedure for determining a confidence interval for gene location by using multipoint linkage analysis. A genetic counselor needs to know the ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Suthers GK,Wilson SR

    更新日期：1990-07-01 00:00:00

  • Education of nurses in genetics.

    abstract：:The need for education of nurses in genetics was articulated more than 25 years ago. This article reviews the knowledge of practicing nurses about genetics as well as the content of genetics in nursing curricula. Implementation of federal legislation that mandated increased availability of genetic services and genetic...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Forsman I

    更新日期：1988-10-01 00:00:00

  • Genetic linkage to chromosome 22q12 for a heavy-smoking quantitative trait in two independent samples.

    abstract：:We conducted a genomewide linkage screen of a simple heavy-smoking quantitative trait, the maximum number of cigarettes smoked in a 24-h period, using two independent samples: 289 Australian and 155 Finnish nuclear multiplex families, all of which were of European ancestry and were targeted for DNA analysis by use of ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/513703

    authors： Saccone SF,Pergadia ML,Loukola A,Broms U,Montgomery GW,Wang JC,Agrawal A,Dick DM,Heath AC,Todorov AA,Maunu H,Heikkila K,Morley KI,Rice JP,Todd RD,Kaprio J,Peltonen L,Martin NG,Goate AM,Madden PA

    更新日期：2007-05-01 00:00:00

  • Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders.

    abstract：:New human mutations are thought to originate in germ cells, thus making a recurrence of the same mutation in a sibling exceedingly rare. However, increasing sensitivity of genomic technologies has anecdotally revealed mosaicism for mutations in somatic tissues of apparently healthy parents. Such somatically mosaic par...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2014.07.003

    authors： Campbell IM,Yuan B,Robberecht C,Pfundt R,Szafranski P,McEntagart ME,Nagamani SC,Erez A,Bartnik M,Wiśniowiecka-Kowalnik B,Plunkett KS,Pursley AN,Kang SH,Bi W,Lalani SR,Bacino CA,Vast M,Marks K,Patton M,Olofsson P,P

    更新日期：2014-08-07 00:00:00

  • Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. I. Statistical methods.

    abstract：:Serum and leukocyte hexosaminidase profiles (total activity and percent heat-labile activity levels) in obligate Sandhoff disease (SHD) heterozygotes differ from those of obligate Tay-Sachs disease (TSD) heterozygotes and noncarrier individuals. We have developed a procedure to identify, with 95% sensitivity, carriers...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Cantor RM,Lim JS,Roy C,Kaback MM

    更新日期：1985-09-01 00:00:00

  • Fine-structure genetic mapping of human chromosomes using the polymerase chain reaction on single sperm: experimental design considerations.

    abstract：:The polymerase chain reaction (PCR) makes it possible to rapidly generate a very large number of copies of a specific region of DNA. Application of PCR to individual human sperm cells permits the typing of a large number of independent male meiotic events. If the donor male is heterozygous at three loci, sperm typing ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Boehnke M,Arnheim N,Li H,Collins FS

    更新日期：1989-07-01 00:00:00

  • Genomewide linkage analysis for internal carotid artery intimal medial thickness: evidence for linkage to chromosome 12.

    abstract：:Carotid intimal medial thickness (IMT) is a heritable quantitative measure of atherosclerosis. A genomewide linkage analysis was conducted to localize a quantitative-trait locus (QTL) influencing carotid IMT. Carotid IMT was measured in 596 men and 629 women from 311 extended families (1,242 sib pairs) in the Framingh...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/381559

    authors： Fox CS,Cupples LA,Chazaro I,Polak JF,Wolf PA,D'Agostino RB,Ordovas JM,O'Donnell CJ

    更新日期：2004-02-01 00:00:00

  • Detection of heterozygotes in maple-syrup-urine disease: measurements of branched-chain alpha-ketoacid dehydrogenase and its components in cell cultures.

    abstract：:To detect heterozygotes for maple-syrup-urine disease (MSUD), activities of branched-chain-alpha-ketoacid (BCKA) dehydrogenase and its components in skin fibroblasts of two obligatory heterozygotes and amnion cells of a fetus at risk were measured. Intact heterozygous cells were found to decarboxylate [1-14C] alpha-ke...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Chuang DT,Ku LS,Kerr DS,Cox RP

    更新日期：1982-05-01 00:00:00

  • Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit.

    abstract：:Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint contractures, pterygia, and respiratory distress. Similar findings occur in newborns exposed to nicotinergic acetylcholine receptor (AChR) antibodies from myasthenic mothers. We performed linkage studies in families with Escobar syndro...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/506257

    authors： Hoffmann K,Muller JS,Stricker S,Megarbane A,Rajab A,Lindner TH,Cohen M,Chouery E,Adaimy L,Ghanem I,Delague V,Boltshauser E,Talim B,Horvath R,Robinson PN,Lochmüller H,Hübner C,Mundlos S

    更新日期：2006-08-01 00:00:00

  • Linkage studies in carriers of Lowe oculo-cerebro-renal syndrome.

    abstract：:A black family with two male infants affected with the X-linked Lowe syndrome was studied. All three females in the pedigree were found to be carriers on the basis of lenticular opacities. Each female had one son. Of these, two were affected and one was unaffected. The Xg blood-group locus and the G6PD locus were dete...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Hittner HM,Carroll AJ,Prchal JT

    更新日期：1982-11-01 00:00:00

  • Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.

    abstract：:N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of t...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2018.03.004

    authors： Cheng H,Dharmadhikari AV,Varland S,Ma N,Domingo D,Kleyner R,Rope AF,Yoon M,Stray-Pedersen A,Posey JE,Crews SR,Eldomery MK,Akdemir ZC,Lewis AM,Sutton VR,Rosenfeld JA,Conboy E,Agre K,Xia F,Walkiewicz M,Longoni M,H

    更新日期：2018-05-03 00:00:00

  • BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2.

    abstract：:In order to evaluate the role of inherited BRCA2 mutations in American families--particularly the appearance in America of European founder mutations--the BRCA2 coding sequence, 5' UTR, and 3' UTR were screened in 22 Caucasian American kindreds with four or more cases of breast or ovarian cancer. Six mutations were fo...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Schubert EL,Lee MK,Mefford HC,Argonza RH,Morrow JE,Hull J,Dann JL,King MC

    更新日期：1997-05-01 00:00:00

  • Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases.

    abstract：:Molecular analysis of the human beta-galactosidase gene revealed six different mutations in 10 of 11 Japanese GM1-gangliosidosis patients. They were the only abnormalities in each allele examined in this study. A 165-nucleotide duplication (positions 1103-1267) was found in two infantile patients, producing an abnorma...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Yoshida K,Oshima A,Shimmoto M,Fukuhara Y,Sakuraba H,Yanagisawa N,Suzuki Y

    更新日期：1991-08-01 00:00:00

  • Trisomy 21: association between reduced recombination and nondisjunction.

    abstract：:To assess the association between recombination and nondisjunction of chromosome 21, we analyzed cytogenetic and DNA markers in 104 trisomy 21 individuals and their parents. Our DNA marker studies of parental origin were informative in 100 cases, with the overwhelming majority (94) being maternal in origin. This value...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Sherman SL,Takaesu N,Freeman SB,Grantham M,Phillips C,Blackston RD,Jacobs PA,Cockwell AE,Freeman V,Uchida I

    更新日期：1991-09-01 00:00:00

  • Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis.

    abstract：:Arthrogryposis multiplex congenita (AMC) is characterized by the presence of multiple joint contractures resulting from reduced or absent fetal movement. Here, we report two unrelated families affected by lethal AMC. By genetic mapping and whole-exome sequencing in a multiplex family, a heterozygous truncating MAGEL2 ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2015.08.010

    authors： Mejlachowicz D,Nolent F,Maluenda J,Ranjatoelina-Randrianaivo H,Giuliano F,Gut I,Sternberg D,Laquerrière A,Melki J

    更新日期：2015-10-01 00:00:00

  • Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3).

    abstract：:Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Eight BBS loci have been mapped, and seven genes have been identified. BBS3 was previously mapped to chr...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/423903

    authors： Chiang AP,Nishimura D,Searby C,Elbedour K,Carmi R,Ferguson AL,Secrist J,Braun T,Casavant T,Stone EM,Sheffield VC

    更新日期：2004-09-01 00:00:00