Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.


:Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOε2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond ε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.


Hum Mutat


Human mutation


McKay GJ,Patterson CC,Chakravarthy U,Dasari S,Klaver CC,Vingerling JR,Ho L,de Jong PT,Fletcher AE,Young IS,Seland JH,Rahu M,Soubrane G,Tomazzoli L,Topouzis F,Vioque J,Hingorani AD,Sofat R,Dean M,Sawitzke J,Seddon




Has Abstract


2011-12-01 00:00:00












  • Disease-causing mutations improving the branch site and polypyrimidine tract: pseudoexon activation of LINE-2 and antisense Alu lacking the poly(T)-tail.

    abstract::Cryptic exons or pseudoexons are typically activated by point mutations that create GT or AG dinucleotides of new 5' or 3' splice sites in introns, often in repetitive elements. Here we describe two cases of tetrahydrobiopterin deficiency caused by mutations improving the branch point sequence and polypyrimidine tract...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Meili D,Kralovicova J,Zagalak J,Bonafé L,Fiori L,Blau N,Thöny B,Vorechovsky I

    更新日期:2009-05-01 00:00:00

  • Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria (DSH).

    abstract::Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis characterized by hyperpigmented and hypopigmented macules of on the extremities and caused by the mutations in the ADAR gene(also called DSRAD) encoding for RNA-specific adenosine deaminase. Here we reported clinical and mol...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zhang XJ,He PP,Li M,He CD,Yan KL,Cui Y,Yang S,Zhang KY,Gao M,Chen JJ,Li CR,Jin L,Chen HD,Xu SJ,Huang W

    更新日期:2004-06-01 00:00:00

  • A mild neurofibromatosis type 1 phenotype produced by the combination of the benign nature of a leaky NF1-splice mutation and the presence of a complex mosaicism.

    abstract::Here we analyze the genetic and molecular basis responsible for a very benign phenotype observed in an NF1 patient. Quantification of cells carrying the NF1 mutation in different samples derived from the three embryonic layers revealed mosaicism. Furthermore, the construction of a minigene with patient's mutation (c.3...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Fernández-Rodríguez J,Castellsagué J,Benito L,Benavente Y,Capellá G,Blanco I,Serra E,Lázaro C

    更新日期:2011-07-01 00:00:00

  • Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations.

    abstract::Hereditary hemorrhagic telangiectasia (HHT), or Osler-Rendu-Weber syndrome, is a heterogeneous inherited disorder characterized by multi-systemic vascular dysplasia and wide variation in its phenotypic expression. Hepatic manifestation is seen in about 8 to 30 % of the patients. The molecular basis for liver involveme...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kuehl HK,Caselitz M,Hasenkamp S,Wagner S,El-Harith el-HA,Manns MP,Stuhrmann M

    更新日期:2005-03-01 00:00:00

  • An XML-based interchange format for genotype-phenotype data.

    abstract::Recent advances in high-throughput genotyping and phenotyping have accelerated the creation of pharmacogenomic data. Consequently, the community requires standard formats to exchange large amounts of diverse information. To facilitate the transfer of pharmacogenomics data between databases and analysis packages, we ha...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Whirl-Carrillo M,Woon M,Thorn CF,Klein TE,Altman RB

    更新日期:2008-02-01 00:00:00

  • An additional mitochondrial tRNA(Ile) point mutation (A-to-G at nucleotide 4295) causing hypertrophic cardiomyopathy.

    abstract::A third point mutation in the mitochondrial tRNA(Ile) gene associated with hypertrophic cardiomyopathy and respiratory chain dysfunction in heart is reported. An A-to-G transition at nucleotide position 4295 was shown to be highly evolutionarily conserved, never present in control individuals, and to segregate with th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Merante F,Myint T,Tein I,Benson L,Robinson BH

    更新日期:1996-01-01 00:00:00

  • Understanding carbamoyl-phosphate synthetase I (CPS1) deficiency by using expression studies and structure-based analysis.

    abstract::Carbamoyl-phosphate synthetase I (CPS1) deficiency (CPS1D), a recessively inherited urea cycle error due to CPS1 gene mutations, causes life-threatening hyperammonemia. The disease-causing potential of missense mutations in CPS1 deficiency can be ascertained with the recombinant CPS1 expression and purification system...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pekkala S,Martínez AI,Barcelona B,Yefimenko I,Finckh U,Rubio V,Cervera J

    更新日期:2010-07-01 00:00:00

  • Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.

    abstract::The Ataxia Telangiectasia Mutation (ATM) gene is mutated in the rare recessive syndrome Ataxia Telangiectasia (AT), which is characterized by cerebellar degeneration, immunodeficiency, and cancer predisposition. In this study, 41 AT families from Denmark, Finland, Norway, and Sweden were screened for ATM mutations. Th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Laake K,Jansen L,Hahnemann JM,Brondum-Nielsen K,Lönnqvist T,Kääriäinen H,Sankila R,Lähdesmäki A,Hammarström L,Yuen J,Tretli S,Heiberg A,Olsen JH,Tucker M,Kleinerman R,Børresen-Dale AL

    更新日期:2000-09-01 00:00:00

  • A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.

    abstract::Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wu X,Katz E,Della Valle MC,Mascioli K,Flanagan JJ,Castelli JP,Schiffmann R,Boudes P,Lockhart DJ,Valenzano KJ,Benjamin ER

    更新日期:2011-08-01 00:00:00

  • Postzygotic single-nucleotide mosaicisms contribute to the etiology of autism spectrum disorder and autistic traits and the origin of mutations.

    abstract::The roles and characteristics of postzygotic single-nucleotide mosaicisms (pSNMs) in autism spectrum disorders (ASDs) remain unclear. In this study of the whole exomes of 2,361 families in the Simons Simplex Collection, we identified 1,248 putative pSNMs in children and 285 de novo SNPs in children with detectable par...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dou Y,Yang X,Li Z,Wang S,Zhang Z,Ye AY,Yan L,Yang C,Wu Q,Li J,Zhao B,Huang AY,Wei L

    更新日期:2017-08-01 00:00:00

  • Mutational and functional analysis of the tumor-suppressor PTPRD in human melanoma.

    abstract::Protein tyrosine phosphatases (PTPs) tightly regulate tyrosine phosphorylation essential for cell growth, adhesion, migration, and survival. We performed a mutational analysis of the PTP gene family in cutaneous metastatic melanoma and identified 23 phosphatase genes harboring somatic mutations. Among these, receptor-...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Walia V,Prickett TD,Kim JS,Gartner JJ,Lin JC,Zhou M,Rosenberg SA,Elble RC,Solomon DA,Waldman T,Samuels Y

    更新日期:2014-11-01 00:00:00

  • Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation.

    abstract::Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. We report the molecular characterization of a de novo balanced t(2;7)(q37.1;q21.3) tr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bocciardi R,Giorda R,Buttgereit J,Gimelli S,Divizia MT,Beri S,Garofalo S,Tavella S,Lerone M,Zuffardi O,Bader M,Ravazzolo R,Gimelli G

    更新日期:2007-07-01 00:00:00

  • Arrays in postnatal and prenatal diagnosis: An exploration of the ethics of consent.

    abstract::The introduction of genome-wide arrays in postnatal and prenatal diagnosis raises challenging ethical issues. Here, we explore questions with regard to the ethics of consent. One important issue is whether informed consent for genome-wide array-based testing is in fact feasible, given the wide range of possible outcom...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dondorp W,Sikkema-Raddatz B,de Die-Smulders C,de Wert G

    更新日期:2012-06-01 00:00:00

  • Denaturing HPLC analysis of DNA deletions and insertions.

    abstract::Denaturing HPLC (DHPLC) is a useful technique for the fast screening of known and unknown heterozygous gene mutations. Most DNA mutations causing genetic disorders consist of nucleotide substitutions, but insertions and deletions occur, albeit less frequently. The heteroduplexes with insertions/deletions have gaps tha...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cremonesi L,Stenirri S,Fermo I,Paroni R,Ferrari M,Cazzola M,Arosio P

    更新日期:2003-07-01 00:00:00

  • Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays.

    abstract::Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytog...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ming JE,Geiger E,James AC,Ciprero KL,Nimmakayalu M,Zhang Y,Huang A,Vaddi M,Rappaport E,Zackai EH,Shaikh TH

    更新日期:2006-05-01 00:00:00

  • Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in Pendred syndrome.

    abstract::Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter). This disorder may account for up to 10% of cases of hereditary deafness. The disease gene (PDS) has been mapped to chromosome 7q22-q31, a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: López-Bigas N,Rabionet R,de Cid R,Govea N,Gasparini P,Zelante L,Arbonés ML,Estivill X

    更新日期:1999-01-01 00:00:00

  • How the TP53 family proteins TP63 and TP73 contribute to tumorigenesis: regulators and effectors.

    abstract::In mammals, the p53 family comprises two additional members, p63 and p73 (hereafter referred to as TP53, TP63, and TP73, respectively). The usage of two alternative promoters produces protein variants either with (transactivating [TA] isoforms) or without (ΔN isoforms) the N-terminal transactivation domain (TAD). In g...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Candi E,Agostini M,Melino G,Bernassola F

    更新日期:2014-06-01 00:00:00

  • Fifth International Mutation Detection Workshop, May 13-16, 1999, Vicoforte, Italy.

    abstract::The Fifth International Mutation Detection Workshop brought together inventors and major users of mutation detection methodology in a freshly refurbished 17(th) century monastery in northern Italy. There were over 120 registrants from 22 nations, all of which gave either a poster or oral presentation, making it diffic...

    journal_title:Human mutation



    authors: Dianzani I,Landegren U,Camaschella C,Ponzone A,Piazza A,Cotton RG

    更新日期:1999-01-01 00:00:00

  • Loss of function of the cytoplasmic isoform of the protein laforin (EPM2A) causes Lafora progressive myoclonus epilepsy.

    abstract::Lafora disease is the most severe teenage-onset progressive epilepsy, a unique form of glycogenosis with perikaryal accumulation of an abnormal form of glycogen, and a neurodegenerative disorder exhibiting an unusual generalized organellar disintegration. The disease is caused by mutations of the EPM2A gene, which enc...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Ianzano L,Young EJ,Zhao XC,Chan EM,Rodriguez MT,Torrado MV,Scherer SW,Minassian BA

    更新日期:2004-02-01 00:00:00

  • A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).

    abstract::Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of I...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sharon D,Ben-Yosef T,Goldenberg-Cohen N,Pras E,Gradstein L,Soudry S,Mezer E,Zur D,Abbasi AH,Zeitz C,Cremers FPM,Khan MI,Levy J,Rotenstreich Y,Birk OS,Ehrenberg M,Leibu R,Newman H,Shomron N,Banin E,Perlman I

    更新日期:2020-01-01 00:00:00

  • The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia.

    abstract::Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN). We screened CN (n = 395) or CyN (n = 92) patients for ELANE mutations and investigated the impact of mutations on mRNA expression, protein expression, and activity. W...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Germeshausen M,Deerberg S,Peter Y,Reimer C,Kratz CP,Ballmaier M

    更新日期:2013-06-01 00:00:00

  • Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis.

    abstract::Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-relate...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Deng Y,Li Z,Liu J,Wang Z,Cao Y,Mou Y,Fu B,Mo B,Wei J,Cheng Z,Luo L,Li J,Shu Y,Wang X,Luo G,Yang S,Wang Y,Zhu J,Yang J,Wu M,Xu X,Ge R,Chen X,Peng Q,Wei G,Li Y,Yang H,Fang S,Zhang X,Xiong W

    更新日期:2018-09-01 00:00:00

  • Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome.

    abstract::Marshall-Smith syndrome (MSS) is a very rare malformation syndrome characterized by typical craniofacial anomalies, abnormal osseous maturation, developmental delay, failure to thrive, and respiratory difficulties. Mutations in the nuclear factor 1/X gene (NFIX) were recently identified as the cause of MSS. In our stu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schanze D,Neubauer D,Cormier-Daire V,Delrue MA,Dieux-Coeslier A,Hasegawa T,Holmberg EE,Koenig R,Krueger G,Schanze I,Seemanova E,Shaw AC,Vogt J,Volleth M,Reis A,Meinecke P,Hennekam RC,Zenker M

    更新日期:2014-09-01 00:00:00

  • Central mutation databases--a review.

    abstract::The Internet has been a key component in the coordination of the diverse group of scientists involved in the Human Genome Project. Nowhere has this contribution been more critical than in the maintenance and exchange of information about genetic variation and mutation. Whereas the majority of DNA sequence is generated...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Porter CJ,Talbot CC,Cuticchia AJ

    更新日期:2000-01-01 00:00:00

  • Characterization of seven novel mutations in seven patients with GAMT deficiency.

    abstract::Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive error of creatine synthesis characterized by cerebral creatine deficiency, accumulation of guanidinoacetate, mental retardation, epilepsy and extrapyramidal signs. So far, six mutations have been identified in seven patients. We investigate...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Item CB,Mercimek-Mahmutoglu S,Battini R,Edlinger-Horvat C,Stromberger C,Bodamer O,Mühl A,Vilaseca MA,Korall H,Stöckler-Ipsiroglu S

    更新日期:2004-05-01 00:00:00

  • Molecular basis of dihydropteridine reductase deficiency.

    abstract::The spectrum of mutations causing dihydropteridine reductase is reviewed. A total of 12 point mutations have been described that map in the DHPR cDNA, resulting in amino acid substitutions, insertions and premature terminations. A further two mutations are described which result in aberrant splicing of DHPR transcript...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Smooker PM,Cotton RG

    更新日期:1995-01-01 00:00:00

  • High throughput detection of microsatellite instability by denaturing high-performance liquid chromatography.

    abstract::Microsatellite instability (MSI) is a hallmark of the DNA replication error phenotype, due to the inactivation of mismatch repair genes. MSI has been implicated in colon and many other gastrointestinal cancers. MSI usually can be analyzed by PCR amplification of microsatellite markers followed by electrophoresis and d...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pan KF,Liu W,Lu YY,Zhang L,Li ZP,Lu WL,Thibodeau SN,You WC

    更新日期:2003-11-01 00:00:00

  • Network-Informed Gene Ranking Tackles Genetic Heterogeneity in Exome-Sequencing Studies of Monogenic Disease.

    abstract::Genetic heterogeneity presents a significant challenge for the identification of monogenic disease genes. Whole-exome sequencing generates a large number of candidate disease-causing variants and typical analyses rely on deleterious variants being observed in the same gene across several unrelated affected individuals...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dand N,Schulz R,Weale ME,Southgate L,Oakey RJ,Simpson MA,Schlitt T

    更新日期:2015-12-01 00:00:00

  • The evaluation of tools used to predict the impact of missense variants is hindered by two types of circularity.

    abstract::Prioritizing missense variants for further experimental investigation is a key challenge in current sequencing studies for exploring complex and Mendelian diseases. A large number of in silico tools have been employed for the task of pathogenicity prediction, including PolyPhen-2, SIFT, FatHMM, MutationTaster-2, Mutat...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Grimm DG,Azencott CA,Aicheler F,Gieraths U,MacArthur DG,Samocha KE,Cooper DN,Stenson PD,Daly MJ,Smoller JW,Duncan LE,Borgwardt KM

    更新日期:2015-05-01 00:00:00

  • Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age at onset of diabetes and deafness.

    abstract::The mitochondrial mutation A3243G has been shown to be associated with a syndrome of diabetes mellitus and sensorineural hearing loss. Using a solid-phase-based sequencing method we have investigated the relation between the proportion of mutant mitochondrial genomes and the time of disease onset among members of thre...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Olsson C,Zethelius B,Lagerström-Fermér M,Asplund J,Berne C,Landegren U

    更新日期:1998-01-01 00:00:00