Abstract:
:Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Tragante V,Barnes MR,Ganesh SK,Lanktree MB,Guo W,Franceschini N,Smith EN,Johnson T,Holmes MV,Padmanabhan S,Karczewski KJ,Almoguera B,Barnard J,Baumert J,Chang YP,Elbers CC,Farrall M,Fischer ME,Gaunt TR,Gho JM,Giegdoi
10.1016/j.ajhg.2013.12.016subject
Has Abstractpub_date
2014-03-06 00:00:00pages
349-60issue
3eissn
0002-9297issn
1537-6605pii
S0002-9297(13)00613-7journal_volume
94pub_type
杂志文章,meta分析abstract::Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants for many complex diseases; however, these variants explain only a small fraction of the heritability. Recently, genetic association studies that leverage external transcriptome data have received much attention and shown...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.03.019
更新日期:2018-05-03 00:00:00
abstract::We report an unusual molecular defect in the mitochondrially encoded ND1 subunit of NADH ubiquinone oxidoreductase (complex I) in a patient with mitochondrial myopathy and isolated complex I deficiency. The mutation is an inversion of seven nucleotides within the ND1 gene, which maintains the reading frame. The invers...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302927
更新日期:2000-06-01 00:00:00
abstract::We report here an evaluation of 55 pregnancies at risk for a sickle hemoglobinopathy prenatally diagnosed by restriction-endonuclease analysis, with the endonucleases MstII and HpaI, of amniocyte DNA. The diagnosis was completed in all cases. Eleven fetuses were predicted to be affected, of which six were terminated. ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Waardenburg syndrome type 4 (WS4), also called Shah-Waardenburg syndrome, is a rare neurocristopathy that results from the absence of melanocytes and intrinsic ganglion cells of the terminal hindgut. WS4 is inherited as an autosomal recessive trait attributable to EDN3 or EDNRB mutations. It is inherited as an autosom...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302895
更新日期:2000-05-01 00:00:00
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
更新日期:2021-01-07 00:00:00
abstract::A current approach to mapping complex-disease-susceptibility loci in genome-wide association (GWA) studies involves leveraging the information in a reference database of dense genotype data. By modeling the patterns of linkage disequilibrium in a reference panel, genotypes not directly measured in the study samples ca...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.01.013
更新日期:2009-02-01 00:00:00
abstract::A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide sc...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/423900
更新日期:2004-09-01 00:00:00
abstract::The genetic map in the region of human chromosome 7 that harbors the gene for cystic fibrosis (CF) has been refined by multilocus linkage studies in an expanded database including a large set of normal families. Six loci known to be linked to CF were examined: MET, an oncogene; COL1A2, collagen, TCRB, T-cell-receptor ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage an...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::The estimate of heterozygosity and proportion of polymorphic loci for 33 red blood cell loci has been updated by the elimination of some loci of questionable status and the addition of data on 33 loci. The new figures for heterozygosity and proportion of polymorphic loci, .105 and .283, respectively, are based on 60 r...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
abstract::Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function. CARD11 encodes an adaptor protein that expresses dominant-negative and gain-of-function variants associated with distinct immunodeficiencies. Here, we used ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.10.015
更新日期:2020-12-03 00:00:00
abstract::X-linked retinitis pigmentosa (XLRP) is a clinically and genetically heterogeneous degenerative disease of the retina. At least five loci have been mapped for XLRP; of these, RP2 and RP3 account for 10%-20% and 70%-90% of genetically identifiable disease, respectively. However, mutations in the respective genes, RP2 a...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/340848
更新日期:2002-06-01 00:00:00
abstract::We report recessive mutations in the gene for the latent transforming growth factor-beta binding protein 4 (LTBP4) in four unrelated patients with a human syndrome disrupting pulmonary, gastrointestinal, urinary, musculoskeletal, craniofacial, and dermal development. All patients had severe respiratory distress, with ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.09.013
更新日期:2009-11-01 00:00:00
abstract::Sensorineural deafness and retinitis pigmentosa (RP) are the hallmarks of Usher syndrome (USH) but are also prominent features in peroxisomal biogenesis defects (PBDs); both are autosomal recessively inherited. The firstborn son of unrelated parents, who both had sensorineural deafness and RP diagnosed as USH, present...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/339766
更新日期:2002-04-01 00:00:00
abstract::The gene for vimentin, an intermediate-filament protein, is growth regulated. We used Southern blot analysis and in situ chromosome hybridization to determine the location of the human vimentin gene. Our results show that there is only one copy of the vimentin gene and that it is located on the short arm of chromosome...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::We performed a genomewide linkage analysis of six separate measurements of body mass index (BMI) taken over a span of 28 years, from 1971 to 1998, in the Framingham Heart Study. Variance-components linkage analysis was performed on 330 families, using 401 polymorphic markers. The number of individuals with data at eac...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/343822
更新日期:2002-11-01 00:00:00
abstract::Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic r...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.04.009
更新日期:2020-06-04 00:00:00
abstract::Uniparental disomy (UPD) is a rare condition in which a diploid offspring carries a chromosomal pair from a single parent. We now report the first two cases of UPD resulting in retinal degeneration. We identified an apparently homozygous loss-of-function mutation of RPE65 (1p31) in one retinal dystrophy patient and an...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338455
更新日期:2002-01-01 00:00:00
abstract::A family with three children with trisomy 21 in which the mother is a phenotypically normal, trisomy 21/normal mosaic was studied. Chromosome 21 fluorescent heteromorphisms were used to document that two of the three number 21's in two of the Down syndrome offspring were of maternal origin. Five cytogenetic surveys in...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Osteogenesis imperfecta (OI) is a heritable disorder that ranges in severity from death in the perinatal period to an increased lifetime risk of fracture. Mutations in COL1A1 and COL1A2, which encode the chains of type I procollagen, result in dominant forms of OI, and mutations in several other genes result in recess...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.02.009
更新日期:2013-04-04 00:00:00
abstract::Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unk...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2016.02.019
更新日期:2016-04-07 00:00:00
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
更新日期:2004-02-01 00:00:00
abstract::Microsatellites are a major type of molecular markers in genetics studies. Their mutational dynamics are not clear. We investigated the patterns and characteristics of 97 mutation events unambiguously identified, from 53 multigenerational pedigrees with 630 subjects, at 362 autosomal dinucleotide microsatellite loci. ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338997
更新日期:2002-03-01 00:00:00
abstract::Prenatal hemoglobinopathy screening was chosen as a model system for the study of patient receptivity to unsolicited genetic information. Providers of prenatal care in Rochester, NY, were offered free testing of all their prenatal patients and genetic counseling of women found positive. The 18,907 prenatal samples tes...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::Genes on chromosomes 17q and 18q have been shown to code for putative tumor suppressors. By a combination of allele-loss studies on sporadic ovarian carcinomas and linkage analysis on a breast/ovarian cancer family, we have investigated the involvement of such genes in these diseases. Allele loss occurred in sporadic ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We use...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.09.007
更新日期:2011-10-07 00:00:00
abstract::We recently reported a two-stage genomewide screen of 48 sib pairs affected with intracranial aneurysms (IAs) that revealed suggestive linkage to chromosome 19q13, with a LOD score of 2.58. The region supporting linkage spanned approximately 22 cM. Here, we report a follow-up study of the locus at 19q13, with a sample...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/382285
更新日期:2004-03-01 00:00:00
abstract::We have investigated the molecular basis for HbH disease in 16 patients from Sardinia, and central and southern Italy. We have shown that HbH disease is produced by the interaction of at least 10 different deletional or nondeletional alpha-thalassemia haplotypes, some of which have been already described in the Medite...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
abstract::A highly-educated, socially aware group of persons presented themselves for Tay-Sachs screening having learned about it mainly from friends, newspapers, radio, and television but not from physicians or rabbis. After learning that screening was possible and deciding that it is in principle a good idea, and after discus...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::Allelic data for the D1S80 locus was obtained by using the PCR and subsequent analysis with a high-resolution, horizontal PAGE technique and silver staining. Compared with RFLP analysis of VNTR loci by Southern blotting, the approach described in this paper offers certain advantages: (1) discrete allele resolution, (2...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00