Abstract：
:Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery rate. Among an approximately 680 known genome-wide association study (GWAS) loci for cardio-metabolic traits, we identified 140 coincident cis-eQTLs at 109 GWAS loci, including 93 eQTLs not previously described. At 49 of these 140 eQTLs, gene expression was nominally associated (p < 0.05) with levels of the GWAS trait. The size of our dataset enabled identification of five loci associated (p < 5 × 10-8) with at least five genes located >5 Mb away. These trans-eQTL signals confirmed and extended the previously reported KLF14-mediated network to 55 target genes, validated the CIITA regulation of class II MHC genes, and identified ZNF800 as a candidate master regulator. Finally, we observed similar expression-clinical trait correlations of genes associated with GWAS loci in both humans and a panel of genetically diverse mice. These results provide candidate genes for further investigation of their potential roles in adipose biology and in regulating cardio-metabolic traits.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Civelek M,Wu Y,Pan C,Raulerson CK,Ko A,He A,Tilford C,Saleem NK,Stančáková A,Scott LJ,Fuchsberger C,Stringham HM,Jackson AU,Narisu N,Chines PS,Small KS,Kuusisto J,Parks BW,Pajukanta P,Kirchgessner T,Collins FS,Gdoi
10.1016/j.ajhg.2017.01.027subject
Has Abstractpub_date
2017-03-02 00:00:00pages
428-443issue
3eissn
0002-9297issn
1537-6605pii
S0002-9297(17)30028-9journal_volume
100pub_type
杂志文章abstract：:With the imminent availability of ultra-high-volume genotyping platforms (on the order of 100,000-1,000,000 genotypes per sample) at a manageable cost, there is growing interest in the possibility of conducting genomewide association studies for a variety of diseases but, so far, little consensus on methods to design ...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1086/432962
更新日期：2005-09-01 00:00:00
abstract：:Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and heritable, in previous studies. As with most psychiatric disorders, examination of pedigrees has not revealed a consistent Mendelian mode of transmission. The response of ADHD patients to medications that inhibit the dopamine transporter...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early dea...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.12.013
更新日期：2015-02-05 00:00:00
abstract：:Eleven normal families with at least four children were studied cytogenetically using the C-band technique to identify polymorphisms in the constitutive heterochromatin of chromosomes 1, 9 and 16. Thirteen individuals showed one or more variants in such chromosomes. The analysis of the segregation ratios in the 35 off...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1976-07-01 00:00:00
abstract：:Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonpa...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/319509
更新日期：2001-04-01 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：:Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance ca...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-10-01 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：:Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have no...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.02.011
更新日期：2012-04-06 00:00:00
abstract：:The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome-wide association s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.11.012
更新日期：2013-01-10 00:00:00
abstract：:Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, a thorough quantification of their overlap in a phenotype-specific manner remains elusive. Here, we have quantified the overlap of genes identified through large-scale genome-wide association studies (GW...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.08.017
更新日期：2018-10-04 00:00:00
abstract：:Quantitative predictions of rates of Down syndrome offspring as a function of maternal serum alpha-fetoprotein (MSAFP) values and of maternal age were reviewed. Comparisons were made of 35-year-equivalent-risk values by maternal age, that is, MSAFP values (at various maternal ages) that predict the risk (of a Down syn...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:mRNA analysis of the cystic fibrosis transmembrane regulator (CFTR) gene in tissues of cystic fibrosis (CF) patients has allowed us to detect a cryptic exon. The new exon involves 49 base pairs between exons 11 and 12 and is due to a point mutation (1811+1.6kbA-->G) that creates a new donor splice site in intron 11. S...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:The connective-tissue disorder occipital horn syndrome (OHS) is hypothesized to be allelic to Menkes disease. The two diseases have different clinical presentations but have a similar abnormality of copper transport. Mice hemizygous for the blotchy allele of the X-linked mottled locus have similar connective-tissue de...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Familial orthostatic hypotensive disorder is characterized by light-headedness on standing, which may worsen to syncope, palpitations, and blue-purple ankle discoloration, and is accompanied by a marked decrease in systolic blood pressure, an increase in diastolic pressure, and tachycardia, all of which resolve when s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302096
更新日期：1998-11-01 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：:Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2017.09.018
更新日期：2017-11-02 00:00:00
abstract：:Recent studies have suggested that a significant fraction of the human genome is contained in blocks of strong linkage disequilibrium, ranging from ~5 to >100 kb in length, and that within these blocks a few common haplotypes may account for >90% of the observed haplotypes. Furthermore, previous studies have suggested...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/382227
更新日期：2004-04-01 00:00:00
abstract：:Keratitis-ichthyosis-deafness syndrome (KID) is a rare ectodermal dysplasia characterized by vascularizing keratitis, profound sensorineural hearing loss (SNHL), and progressive erythrokeratoderma, a clinical triad that indicates a failure in development and differentiation of multiple stratifying epithelia. Here, we ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/339986
更新日期：2002-05-01 00:00:00
abstract：:Despite the growing consensus on the importance of testing gene-gene interactions in genetic studies of complex diseases, the effect of gene-gene interactions has often been defined as a deviance from genetic additive effects, which is essentially treated as a residual term in genetic analysis and leads to low power i...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/508571
更新日期：2006-11-01 00:00:00
abstract：:Previously, we demonstrated evidence of linkage to bipolar affective disorder (BP) in a single large, multigenerational family with a LOD score of 3.41 at the PFKL locus on chromosome 21q22.3. Additional families showed little support for linkage to PFKL under homogeneity or heterogeneity, in that study. We have expan...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302185
更新日期：1999-01-01 00:00:00
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：
更新日期：1992-11-01 00:00:00
abstract：:One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not g...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.05.001
更新日期：2010-06-11 00:00:00
abstract：:Common variation in over 100 genes has been implicated in the risk of developing asthma, but the contribution of rare variants to asthma susceptibility remains largely unexplored. We selected nine genes that showed the strongest signatures of weak purifying selection from among 53 candidate asthma-associated genes, an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.01.008
更新日期：2012-02-10 00:00:00
abstract：:Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogene...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the beta-hexosaminidase A (Hex A) alpha-subunit exon 11 insertion m...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:The identification of genetic variants implicated in human developmental disorders has been revolutionized by second-generation sequencing combined with international pooling of cases. Here, we describe seven individuals who have diverse yet overlapping developmental anomalies, and who all have de novo missense FBXW11...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.07.005
更新日期：2019-09-05 00:00:00
abstract：:Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluate...
journal_title：American journal of human genetics
pub_type： 杂志文章,meta分析
doi：10.1016/j.ajhg.2014.11.011
更新日期：2015-01-08 00:00:00
abstract：:Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.05.023
更新日期：2011-07-15 00:00:00
