Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.


:Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value <0.05 and false discovery rate (FDR) <0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.


Hum Genet


Human genetics


Zhang M,Liang L,Morar N,Dixon AL,Lathrop GM,Ding J,Moffatt MF,Cookson WO,Kraft P,Qureshi AA,Han J




Has Abstract


2012-04-01 00:00:00












  • Trust in genomic data sharing among members of the general public in the UK, USA, Canada and Australia.

    abstract::Trust may be important in shaping public attitudes to genetics and intentions to participate in genomics research and big data initiatives. As such, we examined trust in data sharing among the general public. A cross-sectional online survey collected responses from representative publics in the USA, Canada, UK and Aus...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Milne R,Morley KI,Howard H,Niemiec E,Nicol D,Critchley C,Prainsack B,Vears D,Smith J,Steed C,Bevan P,Atutornu J,Farley L,Goodhand P,Thorogood A,Kleiderman E,Middleton A,Participant Values Work Stream of the Global Allia

    更新日期:2019-12-01 00:00:00

  • Modifier locus of the skeletal muscle involvement in Emery-Dreifuss muscular dystrophy.

    abstract::Autosomal dominant Emery-Dreifuss muscular dystrophy is caused by mutations in LMNA gene encoding lamins A and C. The disease is characterized by early onset joint contractures during childhood associated with humero-peroneal muscular wasting and weakness, and by the development of a cardiac disease in adulthood. Impo...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Granger B,Gueneau L,Drouin-Garraud V,Pedergnana V,Gagnon F,Ben Yaou R,Tezenas du Montcel S,Bonne G

    更新日期:2011-02-01 00:00:00

  • Deficiency, transposition, and duplication of one 15q region may be alternatively associated with Prader-Willi (or a similar) syndrome. Analysis of seven cases after varying ascertainment.

    abstract::Seven patients are described who have some or all of the symptoms of Prader-Willi syndrome. They were ascertained by varying criteria starting either from the clinical picture or from the identification of a chromosome abnormality involving the proximal portion of the long arm of chromosome 15. The chromosome abnormal...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Fraccaro M,Zuffardi O,Bühler E,Schinzel A,Simoni G,Witkowski R,Bonifaci E,Caufin D,Cignacco G,Delendi N

    更新日期:1983-01-01 00:00:00

  • Genetic and epigenetic Muller's ratchet as a mechanism of frailty and morbidity during aging: a demographic genetic model.

    abstract::Mutation accumulation has been proposed as a cause of senescence. During this process, age-related genetic and epigenetic mutations steadily accumulate. Cascading deleterious effects of mutations might initiate a steady "accumulation of deficits" in cells, despite the existence of repair mechanisms, leading to cellula...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Innan H,Veitia R,Govindaraju DR

    更新日期:2020-03-01 00:00:00

  • Chromosome analysis of human sperm. I. First results with a modified method.

    abstract::A modified technique has been developed for the visualization of the chromosomes in human sperm. The cytogenetic analysis of 129 G-banded human sperm metaphases of 6 normal donors showed an incidence of structural and numerical chromosome abnormalities of 7.8%. Two out of 129 spermatozoa were aneuploid (1.6%). The fre...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Jenderny J,Röhrborn G

    更新日期:1987-08-01 00:00:00

  • Mutation analysis of ten exons of the CFTR gene in Greek cystic fibrosis patients: characterization of 74.5% of CF alleles including one novel mutation.

    abstract::To initiate the complete characterization of mutations in the CFTR gene in Greek cystic fibrosis (CF) patients, we screened 184 patients for six relatively common mutations (delta F 508, G542X, G551D, 621 + 1 G-->T, N1303K, W1282X) using allele-specific hybridization and, in addition, analyzed exons 4, 5, 7, 8, 10, 11...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Kanavakis E,Tzetis M,Antoniadi T,Traeger-Synodinos J,Doudounakis S,Adam G,Matsaniotis N,Kattamis C

    更新日期:1995-09-01 00:00:00

  • Reexamination of paternal age effect in Down's syndrome.

    abstract::The recent discovery that the extra chromosome in about 30% of cases of 47, trisomy 21 is of paternal origin has revived interest in the possibility of paternal age as a risk factor for a Down syndrome birth, independent of maternal age. Parental age distribution for 611 Down's syndrome 47, +21 cases was studied. The ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Roth MP,Feingold J,Baumgarten A,Bigel P,Stoll C

    更新日期:1983-01-01 00:00:00

  • High resolution multicolor fluorescence in situ hybridization using cyanine and fluorescein dyes: rapid chromosome identification by directly fluorescently labeled alphoid DNA probes.

    abstract::We tested DNA probes directly labeled by fluorescently labeled nucleotides (Cy3-dCTP, Cy5-dCTP, FluorX-dCTP) for high resolution uni- and multicolor detection of human chromosomes and analysis of centromeric DNA organization by in situ hybridization. Alpha-satellite DNA probes specific to chromosomes 1, 2, 3, 4 + 9, 5...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Yurov YB,Soloviev IV,Vorsanova SG,Marcais B,Roizes G,Lewis R

    更新日期:1996-03-01 00:00:00

  • Genetic fine mapping of the gene for recessive Stargardt disease.

    abstract::Stargardt disease (STGD) is one of the most frequent causes of macular degeneration in childhood. Linkage analysis in families with recessive STGD has recently shown genetic homogeneity and a location of the underlying gene at 1p22-p21 in a 4-cM interval. Haplotype analysis in seven Dutch STGD families with 11 highly ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Hoyng CB,Poppelaars F,van de Pol TJ,Kremer H,Pinckers AJ,Deutman AF,Cremers FP

    更新日期:1996-10-01 00:00:00

  • Assignment of human plasma methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase or chitinase to chromosome 1q by a linkage study.

    abstract::Plasma methylumbelliferyl tetra-N-acetylchitotetraoside hydrolase or chitinase (CHIT) might play a role in degrading the chitin wall of some microorganisms. In about 6% of Caucasian people the enzyme shows pseudodeficiency (defined as very low activity without apparent symptoms). We have mapped this locus by linkage a...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Eiberg H,Den Tandt WR

    更新日期:1997-12-01 00:00:00

  • TaqI HLA-B and -DRB RFLP analysis can predict disease in siblings of affected children with 21-hydroxylase deficiency.

    abstract::The possibility of using TaqI restriction fragment length polymorphism (RFLP) analysis of the HLA-B locus and the HLA-DR-DQ subregions, flanking the 21-hydroxylase genes, for predicting disease in siblings of children with 21-hydroxylase deficiency was analyzed in 12 nuclear families with at least one affected child a...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Olerup O,Luthman H,Ritzén EM,Haglund-Stengler B

    更新日期:1990-10-01 00:00:00

  • Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics.

    abstract::While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more e...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Schaid DJ,McDonnell SK,Zarfas KE,Cunningham JM,Hebbring S,Thibodeau SN,Eeles RA,Easton DF,Foulkes WD,Simard J,Giles GG,Hopper JL,Mahle L,Moller P,Badzioch M,Bishop DT,Evans C,Edwards S,Meitz J,Bullock S,Hope Q,G

    更新日期:2006-11-01 00:00:00

  • Exploiting the proteome to improve the genome-wide genetic analysis of epistasis in common human diseases.

    abstract::One of the central goals of human genetics is the identification of loci with alleles or genotypes that confer increased susceptibility. The availability of dense maps of single-nucleotide polymorphisms (SNPs) along with high-throughput genotyping technologies has set the stage for routine genome-wide association stud...

    journal_title:Human genetics

    pub_type: 杂志文章,评审


    authors: Pattin KA,Moore JH

    更新日期:2008-08-01 00:00:00

  • Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

    abstract::Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Eising E,Huisman SMH,Mahfouz A,Vijfhuizen LS,Anttila V,Winsvold BS,Kurth T,Ikram MA,Freilinger T,Kaprio J,Boomsma DI,van Duijn CM,Järvelin MR,Zwart JA,Quaye L,Strachan DP,Kubisch C,Dichgans M,Davey Smith G,Stefansso

    更新日期:2016-04-01 00:00:00

  • Ways of improving precise knock-in by genome-editing technologies.

    abstract::Despite the recent discover of genome-editing methods, today we can say these approaches have firmly entered our life. Two approaches-knocking out malfunctioning gene allele or correcting the mutation with precise knock-in-can be used in hereditary monogenic diseases treatment. The latter approach is relatively ineffe...

    journal_title:Human genetics

    pub_type: 杂志文章,评审


    authors: Smirnikhina SA,Anuchina AA,Lavrov AV

    更新日期:2019-01-01 00:00:00

  • Evidence for a major gene (RP10) for autosomal dominant retinitis pigmentosa on chromosome 7q: linkage mapping in a second, unrelated family.

    abstract::Retinitis pigmentosa is a genetically heterogeneous form of retinal degeneration, which has X-linked, autosomal recessive and autosomal dominant forms. The disease genes in families with autosomal dominant retinitis pigmentosa (adRP) have been linked to six loci, on 3q, 6p, 7p, 7q, 8q and 19q. In a large American fami...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: McGuire RE,Gannon AM,Sullivan LS,Rodriguez JA,Daiger SP

    更新日期:1995-01-01 00:00:00

  • Molecular analysis of chromosome region 11p13 in patients with Drash syndrome.

    abstract::The association of nephropathy, Wilms' tumour and genital abnormalities is known as Drash syndrome. Two of these features are also seen in the WAGR (Wilms' tumour, aniridia, genito-urinary abnormalities, mental retardation) complex, known to be associated with deletions of chromosome region 11p13. We have carried out ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Jadresic L,Wadey RB,Buckle B,Barratt TM,Mitchell CD,Cowell JK

    更新日期:1991-03-01 00:00:00

  • KATP channel Kir6.2 E23K variant overrepresented in human heart failure is associated with impaired exercise stress response.

    abstract::ATP-sensitive K+ (K(ATP)) channels maintain cardiac homeostasis under stress, as revealed by murine gene knockout models of the KCNJ11-encoded Kir6.2 pore. However, the translational significance of K(ATP) channels in human cardiac physiology remains largely unknown. Here, the frequency of the minor K23 allele of the ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Reyes S,Park S,Johnson BD,Terzic A,Olson TM

    更新日期:2009-12-01 00:00:00

  • New polymorphisms and markers in the HLA class I region: relevance to hereditary hemochromatosis (HFE).

    abstract::Hereditary hemochromatosis (HFE) is an inherited disorder whose gene lies in the proximity of the histocompatibility antigen (HLA) class I region, on 6p21.3. Despite efforts in refining the HFE region, a number of informative DNA markers, linked to the disease locus and amenable to use in an assay based on the polymer...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Totaro A,Grifa A,Roetto A,Lunardi C,D'Agruma L,Sbaiz L,Zelante L,De Sandre G,Camaschella C,Gasparini P

    更新日期:1995-04-01 00:00:00

  • Assignment of the human ST2 gene to chromosome 2 at q11.2.

    abstract::The human St2 locus has been assigned to chromosome 2, using a human ST2 cDNA clone, by a human/rodent somatic cel hybrid mapping panel. The St2 locus has also been mapped to chromosome 2q11.2, using a human ST2 genomic DNA clone, by in situ hybridization. The locus is very tightly linked to the Il-1r1 locus. Together...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Tominaga S,Inazawa J,Tsuji S

    更新日期:1996-05-01 00:00:00

  • Familial benign hypercalcaemia (FBH; McK. No. 14598, 1983): linkage studies in a large Dutch family.

    abstract::By screening 27 hypercalcaemic and 21 normocalcaemic subjects in a large Dutch pedigree with familial benign hypercalcaemia (FBH; McK. No. 14598) (McKusick 1983) for more than 35 genetic markers, it was found that linkage of FBH can be excluded at about 25 centimorgans (cM) from GM, 20 cM from ABO, 15 cM from MNS and ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Menko FH,Bijvoet OL,Meera Khan P,Nijenhuis LE,von Loghem E,Schreuder I,Bernini LF,Pronk JC,Madan K,Went LN

    更新日期:1984-01-01 00:00:00

  • Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8.

    abstract::Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2. We identified a dominant missense mutation, c.3235G>A in COL1A1 exon 45 predicting p.G1079S, in a Japanese family with mild OI. As mutations in exon 45 exhibit mild to lethal phenotypes, we tested if disruption of an exonic spl...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Kaneko H,Kitoh H,Matsuura T,Masuda A,Ito M,Mottes M,Rauch F,Ishiguro N,Ohno K

    更新日期:2011-11-01 00:00:00

  • A haplotype at chromosome Xq27.2 confers susceptibility to prostate cancer.

    abstract::We conducted an association study to identify risk variants for familial prostate cancer within the HPCX locus at Xq27 among Americans of Northern European descent. We investigated a total of 507 familial prostate cancer probands and 507 age-matched controls without a personal or family history of prostate cancer. The...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Yaspan BL,McReynolds KM,Elmore JB,Breyer JP,Bradley KM,Smith JR

    更新日期:2008-05-01 00:00:00

  • Replication status of the fragile X chromosome, fra(X)(q27), in three heterozygous females.

    abstract::Investigation of lymphocyte cultures from three females heterozygous for fra(X)(q27) shows widely differing proportions of early and late replicating X chromosomes having the fragile site, and suggests that the replication status of the fragile X may be related to the mental capacity of the patient. The study has util...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Howell RT,McDermott A

    更新日期:1982-01-01 00:00:00

  • Translocation t(1;17)(q12;q25) with a clinical picture like of a proximal deletion of 1q: identification by in situ hybridization with chromosome 1-specific satellite DNA probes.

    abstract::The authors report a case of a balanced 1;17 translocation with breakpoints located in the secondary constriction of chromosome 1. This translocation is associated with pathological symptoms similar to those observed following a proximal deletion of 1q. We request contact with colleques who have observed similar, or r...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Vorsanova SG,Yurov YB,Kurbatov MB,Kazantzeva LZ

    更新日期:1990-12-01 00:00:00

  • High-resolution array-CGH profiling of germline and tumor-specific copy number alterations on chromosome 22 in patients affected with schwannomas.

    abstract::Schwannomas may develop sporadically or in association with NF2 and schwannomatosis. The fundamental aberration in schwannomas is the bi-allelic inactivation of the NF2 gene. However, clinical and molecular data suggest that these tumors share a common pathogenetic mechanism related to as yet undefined 22q-loci. Linka...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Díaz de Ståhl T,Hansson CM,de Bustos C,Mantripragada KK,Piotrowski A,Benetkiewicz M,Jarbo C,Wiklund L,Mathiesen T,Nyberg G,Collins VP,Evans DG,Ichimura K,Dumanski JP

    更新日期:2005-10-01 00:00:00

  • Identification, mapping, and genomic structure of a novel X-chromosomal human gene (SMPX) encoding a small muscular protein.

    abstract::Reciprocal probing has been used to identify a cDNA clone (xh8H11) representing a gene preferentially expressed in striated muscle. The gene maps close to DXS7101 31.9 cM from the short arm telomere of the X-chromosome at Xp22.1. On searching expressed and genomic databases, 21 expressed sequence tags were found that ...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Patzak D,Zhuchenko O,Lee CC,Wehnert M

    更新日期:1999-11-01 00:00:00

  • Two new mutations in the sterol 27-hydroxylase gene in two families lead to cerebrotendinous xanthomatosis.

    abstract::This report concerns two new mutations in the sterol 27-hydroxylase gene in two patients with cerebrotendinous xanthomatosis (CTX). In a Surinam-Creole patient (patient A), a G deletion on position cDNA 546/547 in exon 3 led to a frameshift and the introduction of a premature termination codon. In a Dutch patient (pat...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Verrips A,Steenbergen-Spanjers GC,Luyten JA,van den Heuvel LP,Keyser A,Gabreëls FJ,Wevers RA

    更新日期:1996-12-01 00:00:00

  • Biobanks and the phantom public.

    abstract::This paper surveys the current state of knowledge about the relationship between different national publics and biobanks, how different publics perceive biobanks, and which issues are identified as important by various stakeholders. We discuss existing studies and emerging governance strategies dealing with the bioban...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Gottweis H,Chen H,Starkbaum J

    更新日期:2011-09-01 00:00:00

  • Combined action of isoniazid and para-aminosalicylic acid in vivo on human chromosomes in lymphocyte cultures.

    abstract::Two antitubercular drugs, viz., isoniazid (INH) and para-aminosalicylic acid (PAS), in combination, were evaluated for their in vivo clastogenic effects of human lymphocyte chromosomes. Lymphocyte cultures from tuberculosis patients taking a therapeutic dose of INH and PAS for a period of not less than 3 months and fr...

    journal_title:Human genetics

    pub_type: 杂志文章


    authors: Jaju M,Jaju M,Ahuja YR

    更新日期:1981-01-01 00:00:00