Genetic-risk assessment of GWAS-derived susceptibility loci for type 2 diabetes in a 10 year follow-up of a population-based cohort study.

Abstract:

:To date, genome-wide meta-analyses have identified genetic susceptibility to type 2 diabetes mellitus (T2D) predominantly in populations of European ancestry. However, comprehensive genetic-risk assessment based on previous GWAS loci has not been fully tested in non-European populations. To evaluate whether a genetic-risk score (GRS) could improve T2D-risk prediction in the Korean population, a GRS (GRS-55) was constructed by summing 55 risk alleles based on the 1000 Genomes imputation in the Korean Association Resource study (T2D cases=1042 and controls=2943 at baseline). We also constructed another GRS (GRS-19) based on nominal significance and consistent direction of effect. In mean difference tests, the mean value of the GRS-19 was significantly higher in T2D cases than in controls at baseline examination. In a model adjusted for area, age, sex and body mass index, weighted GRS-19 was found to be associated with enhanced effect sizes of T2D risk under consistent C-statistics. In addition, we confirmed cumulative risk effects on incidence rates of T2D, fasting plasma glucose and glycated hemoglobin (HbA1c) levels in a longitudinal 10 year of follow-up study. These findings highlight that a genotype score comprised of 19 common variants contributed to T2D-risk prediction in the Korean population. Further multi-locus epistatic interactions may provide the possibility to improve risk prediction in C-statistics for discrimination or reclassification.

journal_name

J Hum Genet

authors

Go MJ,Lee Y,Park S,Kwak SH,Kim BJ,Lee J

doi

10.1038/jhg.2016.93

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

1009-1012

issue

12

eissn

1434-5161

issn

1435-232X

pii

jhg201693

journal_volume

61

pub_type

杂志文章
  • Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency.

    abstract::In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recomb...

    journal_title:Journal of human genetics

    pub_type: 杂志文章,评审

    doi:10.1038/jhg.2016.46

    authors: Saito S,Kurosawa A,Adachi N

    更新日期:2016-08-01 00:00:00

  • Tandem configurations of variably duplicated segments of 22q11.2 confirmed by fiber-FISH analysis.

    abstract::22q11.2 duplication syndrome has recently been established as a new syndrome manifesting broad clinical phenotypes including mental retardation. It is reciprocal to DiGeorge (DGS)/velo-cardio-facial syndrome (VCFS), in which the same portion of the chromosome is hemizygously deleted. Deletions and duplications of the ...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2011.100

    authors: Shimojima K,Okamoto N,Inazu T,Yamamoto T

    更新日期:2011-11-01 00:00:00

  • Tissue specificity of methylation and expression of human genes coding for neuropeptides and their receptors, and of a human endogenous retrovirus K family.

    abstract::The purpose of the present study was to understand the tissue specificity of DNA methylation and the relationship between methylation and expression of genes with essential roles in neurodevelopment and brain function. We chose dopamine receptor genes (DRD1 and DRD2), NCAM, and COMT as examples of genes with CpG islan...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s10038-006-0382-9

    authors: Shen HM,Nakamura A,Sugimoto J,Sakumoto N,Oda T,Jinno Y,Okazaki Y

    更新日期:2006-01-01 00:00:00

  • A PDE3A mutation in familial hypertension and brachydactyly syndrome.

    abstract::Hypertension and brachydactyly syndrome (HTNB) with short stature is an autosomal-dominant disorder. Mutations in the PDE3A gene located at 12p12.2-p11.2 were recently identified in HTNB families. We found a novel heterozygous missense mutation c.1336T>C in exon 4 of the PDE3A gene in a Japanese family with multiple H...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2016.32

    authors: Boda H,Uchida H,Takaiso N,Ouchi Y,Fujita N,Kuno A,Hata T,Nagatani A,Funamoto Y,Miyata M,Yoshikawa T,Kurahashi H,Inagaki H

    更新日期:2016-08-01 00:00:00

  • PlexinA polymorphisms mediate the developmental trajectory of human corpus callosum microstructure.

    abstract::PlexinA is a neuronal receptor protein that facilitates axon guidance during embryogenesis. This gene is associated with several neurological disorders including Alzheimer's disease, Parkinson's disease and autism. However, the effect of variants of PlexinA on brain structure remains unclear. We demonstrate that singl...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2014.107

    authors: Belyk M,Kraft SJ,Brown S,Pediatric Imaging, Neurocognition and Genetics Study.

    更新日期:2015-03-01 00:00:00

  • A grid-search algorithm for optimal allocation of sample size in two-stage association studies.

    abstract::Multiple testing occurs commonly in genome-wide association studies with dense SNPs map. With numerous SNPs, not only the genotyping cost and time increase dramatically, many family wise error rate (FWER) controlling methods may fail for being too conservative and of less power when detecting SNPs associated with dise...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s10038-007-0159-9

    authors: Wen SH,Hsiao CK

    更新日期:2007-01-01 00:00:00

  • Clinical applications of two-color telomeric fluorescence in situ hybridization for prenatal diagnosis: identification of chromosomal translocation in five families with recurrent miscarriages or a child with multiple congenital anomalies.

    abstract::Two-color fluorescence in situ hybridization (FISH) analysis using human chromosome arm-specific telomeric probes (telomeric probes) was used successfully to detect each derivative chromosome of a translocation carrier in five couples who requested a prenatal diagnosis in future pregnancies. Most of the human chromoso...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s100380050115

    authors: Wakui K,Tanemura M,Suzumori K,Hidaka E,Ishikawa M,Kubota T,Fukushima Y

    更新日期:1999-01-01 00:00:00

  • A pilot study of gene testing of genetic bone dysplasia using targeted next-generation sequencing.

    abstract::Molecular diagnosis of genetic bone dysplasia is challenging for non-expert. A targeted next-generation sequencing technology was applied to identify the underlying molecular mechanism of bone dysplasia and evaluate the contribution of these genes to patients with bone dysplasia encountered in pediatric endocrinology....

    journal_title:Journal of human genetics

    pub_type: 临床试验,杂志文章

    doi:10.1038/jhg.2015.112

    authors: Zhang H,Yang R,Wang Y,Ye J,Han L,Qiu W,Gu X

    更新日期:2015-12-01 00:00:00

  • Genetic polymorphism of nonsyndromic cleft lip with or without cleft palate is associated with developmental dyslexia in Chinese school-aged populations.

    abstract::Developmental dyslexia (DD) is a neurodevelopment disorder characterized by reading disabilities without apparent etiologies. Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a structural craniofacial malformation featured by isolated orofacial abnormalities. Despite substantial phenotypic differences, ...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2016.121

    authors: Wang B,Zhou Y,Leng S,Zheng L,Lv H,Wang F,Tan LH,Sun Y

    更新日期:2017-02-01 00:00:00

  • Quantifying the uncertainty in heritability.

    abstract::The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2014.15

    authors: Furlotte NA,Heckerman D,Lippert C

    更新日期:2014-05-01 00:00:00

  • The genomic landscape of human immune-mediated diseases.

    abstract::As the methodology of genetic detection has developed rapidly in recent years, through techniques such as genome-wide association studies (GWAS) and the secondary generation of sequencing, we are able to view the genomic landscape more clearly. It is well known that genes have a vital role in the pathogenesis of immun...

    journal_title:Journal of human genetics

    pub_type: 杂志文章,评审

    doi:10.1038/jhg.2015.99

    authors: Wu X,Chen H,Xu H

    更新日期:2015-11-01 00:00:00

  • De novo 617G-A nucleotide mutation in the ACVR1 gene in a Taiwanese patient with fibrodysplasia ossificans progressiva.

    abstract::Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease with autosomal dominant transmission characterized by the presence of malformations of the big toes and of postnatal progressive heterotopic endochondral osteogenesis. We report the case of 3-year-old girl with dysplasia of the first metatarsal b...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s10038-006-0069-2

    authors: Lin GT,Chang HW,Liu CS,Huang PJ,Wang HC,Cheng YM

    更新日期:2006-01-01 00:00:00

  • Identification of three missense mutations in the peroxisome proliferator-activated receptor alpha gene in Japanese subjects with maturity-onset diabetes of the young.

    abstract::We screened the protein-coding region of the peroxisome proliferator-activated receptor alpha gene (PPARA) and the flanking intron sequences for mutations in 57 unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three missense mutations, designated P22R, D140Y, and V227A. The D140Y ...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s100380170080

    authors: Hara M,Wang X,Paz VP,Iwasaki N,Honda M,Iwamoto Y,Bell GI

    更新日期:2001-01-01 00:00:00

  • Detection of novel Y SNPs provides further insights into Y chromosomal variation in Pakistan.

    abstract::Biallelic polymorphisms on the Y chromosome have been extensively used to study the history, evolution, and migration patterns of world populations. In this study we screened 8.5 kb of Y chromosomal DNA for single nucleotide polymorphisms (SNPs) in a panel of 95 male individuals belonging to different haplogroups. Fiv...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s10038-005-0357-2

    authors: Mohyuddin A,Ayub Q,Underhill PA,Tyler-Smith C,Mehdi SQ

    更新日期:2006-01-01 00:00:00

  • Co-segregation of elevated LDL with a novel mutation (D92K) of the LDL receptor in a kindred with multiple lipoprotein abnormalities.

    abstract::Factors predisposing to the phenotypic features of familial combined hyperlipidemia have not been clearly defined. In the course of investigating familial coronary artery disease in Utah, we identified a three-generation family in which multiple members were affected with type IIa hyperlipoproteinemia (HLP IIa), type ...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s100380050202

    authors: Wu LL,Hopkins PN,Xin Y,Stephenson SH,Williams RR,Nobe Y,Kajita M,Nakajima T,Emi M

    更新日期:2000-01-01 00:00:00

  • Identification of a novel human DDX40gene, a new member of the DEAH-box protein family.

    abstract::The DExH/D-box superfamily of RNA helicases seems to play key roles during RNA metabolism, such as pre-mRNA splicing, ribosome biogenesis, and others. We have cloned a new gene of the DEAH-box protein subgroup, designated DDX40 (DEAD/H-box polypeptide 40 gene). DDX40 contains 3656 nucleotides and codes for a putative ...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s100380200104

    authors: Xu J,Wu H,Zhang C,Cao Y,Wang L,Zeng L,Ye X,Wu Q,Dai J,Xie Y,Mao Y

    更新日期:2002-01-01 00:00:00

  • Genetic differences in the two main groups of the Japanese population based on autosomal SNPs and haplotypes.

    abstract::Although the Japanese population has a rather low genetic diversity, we recently confirmed the presence of two main clusters (the Hondo and Ryukyu clusters) through principal component analysis of genome-wide single-nucleotide polymorphism (SNP) genotypes. Understanding the genetic differences between the two main clu...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2012.26

    authors: Yamaguchi-Kabata Y,Tsunoda T,Kumasaka N,Takahashi A,Hosono N,Kubo M,Nakamura Y,Kamatani N

    更新日期:2012-05-01 00:00:00

  • Genome-wide association studies in Samoans give insight into the genetic architecture of fasting serum lipid levels.

    abstract::The current understanding of the genetic architecture of lipids has largely come from genome-wide association studies (GWAS). To date, few GWAS have examined the genetic architecture of lipids in Polynesians, and none have in Samoans, whose unique population history, including many population bottlenecks, may provide ...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/s10038-020-0816-9

    authors: Carlson JC,Weeks DE,Hawley NL,Sun G,Cheng H,Naseri T,Reupena MS,Tuitele J,Deka R,McGarvey ST,Minster RL

    更新日期:2021-02-01 00:00:00

  • Genomic structure of the gene encoding human 3-hydroxy-3-methyl-glutaryl coenzyme A reductase: comparison of exon/intron organization of sterol-sensing domains among four related genes.

    abstract::We determined the genomic structure of the human gene encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate and is the rate-limiting and major regulatory enzyme in sterol biosynthesis. The gene is more than 21 kb long, about five times the size of i...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s100380070017

    authors: Nakajima T,Iwaki K,Hamakubo T,Kodama T,Emi M

    更新日期:2000-01-01 00:00:00

  • Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene.

    abstract::The alpha 2-adrenergic receptors (alpha2-AR) mediate physiological effects of epinephrine and norepinephrine. Three genes encode alpha2-AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325). We genotyped these functional markers plus a panel of single ...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s10038-004-0211-y

    authors: Belfer I,Buzas B,Hipp H,Phillips G,Taubman J,Lorincz I,Evans C,Lipsky RH,Enoch MA,Max MB,Goldman D

    更新日期:2005-01-01 00:00:00

  • Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis.

    abstract::Ectopic periarticular calcifications associated with elevated levels of serum phosphate represent the principal clinical features of hyperphosphatemic familial tumoral calcinosis (HFTC), a rare autosomal recessive metabolic disorder. The disease can be caused by recessive mutations in at least two different genes: Gal...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s10038-007-0126-5

    authors: Barbieri AM,Filopanti M,Bua G,Beck-Peccoz P

    更新日期:2007-01-01 00:00:00

  • Transitional change in interaction between HIF-1 and HNF-4 in response to hypoxia.

    abstract::The roles of the erythropoietin (Epo) 3' enhancer in the activation of gene expression in response to hypoxia were investigated. The enhancer contains hypoxia-inducible enhancer binding site 1 (HIF-1 element) and two direct repeats of hexanucleotide consensus nuclear receptor half site (HNF-4 element). HIF-1, which is...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1007/s100380050163

    authors: Zhang W,Tsuchiya T,Yasukochi Y

    更新日期:1999-01-01 00:00:00

  • A genetic-phenotypic classification for syndromic micrognathia.

    abstract::Micrognathia is a common craniofacial deformity which represents hypoplastic development of the mandible, accompanied by retrognathia and consequent airway problems. Usually, micrognathia is accompanied by multiple systematic defects, known as syndromic micrognathia, and is in close association with genetic factors. N...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/s10038-019-0630-4

    authors: Chen Q,Zhao Y,Qian Y,Lu C,Shen G,Dai J

    更新日期:2019-09-01 00:00:00

  • HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves' disease.

    abstract::Graves' disease (GD) is an autoimmune disease characterized by hyperthyroidism due to the presence of autoantibodies against thyroid-stimulating hormone receptor, which is measured as thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII). Most of the GD patients are TBII-positive, but TBII is undetectab...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2010.20

    authors: Takahashi M,Kimura A

    更新日期:2010-05-01 00:00:00

  • A unique demographic history exists for the MAO-A gene in Polynesians.

    abstract::Variation in the human monoamine oxidase A (MAO-A) gene can influence neurotransmittor levels and is thought to have a role in many behavioral traits. The genetic architecture of MAO-A is known to vary across different geographic subgroups. Previous studies have reported evidence for positive selection within the MAO-...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2012.19

    authors: Eccles DA,Macartney-Coxson D,Chambers GK,Lea RA

    更新日期:2012-05-01 00:00:00

  • Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome: rs17884724:A>C is associated with 7-alanine expansion.

    abstract::With congenital central hypoventilation syndrome (CCHS), most patients have a de novo 5-13 polyalanine expansion mutation in PHOX2B. We reported previously that de novo polyalanine expansion mutations were of paternal origin and were derived from unequal sister chromatid exchange during spermatogenesis in six and four...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2009.109

    authors: Arai H,Otagiri T,Sasaki A,Umetsu K,Hayasaka K

    更新日期:2010-01-01 00:00:00

  • Hair roots as an mRNA source for mutation analysis of Usher syndrome-causing genes.

    abstract::mRNA is an important tool to study the effects of particular mutations on the mode of splicing and transcripts. However, it is often difficult to isolate mRNA because the organ or tissue in which the gene is expressed cannot be sampled. We previously identified two probable splicing mutations (c.6485+5G>A and c.8559-2...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2010.83

    authors: Nakanishi H,Ohtsubo M,Iwasaki S,Hotta Y,Mizuta K,Mineta H,Minoshima S

    更新日期:2010-10-01 00:00:00

  • Erratum to: Huntington disease mutation in Venezuela: age of onset, haplotype analyses and geographic aggregation.

    abstract::In Table 2, a column heading was inadvertently omitted. Corrected table is as follows. ...

    journal_title:Journal of human genetics

    pub_type: 已发布勘误

    doi:10.1007/s10038-008-0256-4

    authors: Paradisi I,Hernández A,Arias S

    更新日期:2008-04-01 00:00:00

  • Correction to: DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Journal of human genetics

    pub_type: 已发布勘误

    doi:10.1038/s10038-020-00867-w

    authors: Terasaki A,Nakamura M,Urata Y,Hiwatashi H,Yokoyama I,Yasuda T,Onuma T,Wada K,Kaneko S,Kan R,Niwa SI,Hashimoto O,Komure O,Goto YI,Yamagishi Y,Nakano M,Furusawa Y,Sano A

    更新日期:2020-11-13 00:00:00

  • Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies.

    abstract::A few mutations in the gene encoding the gamma 2 subunit of the gamma-aminobutyric acid receptor type A (GABRG2) have been reported in various types of epilepsy. The aim of this study is to investigate the role of GABRG2 in the pathogenesis of childhood epilepsy in a large Japanese cohort. Genetic analysis of GABRG2 w...

    journal_title:Journal of human genetics

    pub_type: 杂志文章

    doi:10.1038/jhg.2010.47

    authors: Shi X,Huang MC,Ishii A,Yoshida S,Okada M,Morita K,Nagafuji H,Yasumoto S,Kaneko S,Kojima T,Hirose S

    更新日期:2010-06-01 00:00:00