Abstract:
:Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Graff M,Scott RA,Justice AE,Young KL,Feitosa MF,Barata L,Winkler TW,Chu AY,Mahajan A,Hadley D,Xue L,Workalemahu T,Heard-Costa NL,den Hoed M,Ahluwalia TS,Qi Q,Ngwa JS,Renström F,Quaye L,Eicher JD,Hayes JE,Cornelidoi
10.1371/journal.pgen.1006528subject
Has Abstractpub_date
2017-04-27 00:00:00pages
e1006528issue
4eissn
1553-7390issn
1553-7404pii
PGENETICS-D-16-01816journal_volume
13pub_type
杂志文章,meta分析相关文献
PLoS Genetics文献大全abstract::Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 an...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005503
更新日期:2015-09-10 00:00:00
abstract::Papillorenal syndrome (PRS, also known as renal-coloboma syndrome) is an autosomal dominant disease characterized by potentially-blinding congenital optic nerve excavation and congenital kidney abnormalities. Many patients with PRS have mutations in the paired box transcription factor gene, PAX2. Although most mutatio...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000870
更新日期:2010-03-05 00:00:00
abstract::The sterol regulatory element-binding protein (SREBP) family member SREBP1 is a critical transcriptional regulator of cholesterol and fatty acid metabolism and has been implicated in insulin resistance, diabetes, and other diet-related diseases. We globally identified the promoters occupied by SREBP1 and its binding p...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000133
更新日期:2008-07-25 00:00:00
abstract::NF-κB is a key transcription factor regulating the expression of inflammatory responsive genes. How NF-κB binds to naked DNA templates is well documented, but how it interacts with chromatin is far from being clear. Here we used a combination of UV laser footprinting, hydroxyl footprinting and electrophoretic mobility...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003830
更新日期:2013-01-01 00:00:00
abstract::The differentiation of cells into distinct cell types, each of which is heritable for many generations, underlies many biological phenomena. White and opaque cells of the fungal pathogen Candida albicans are two such heritable cell types, each thought to be adapted to unique niches within their human host. To systemat...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001070
更新日期:2010-08-19 00:00:00
abstract::Knowledge of biological relatedness between samples is important for many genetic studies. In large-scale human genetic association studies, the estimated kinship is used to remove cryptic relatedness, control for family structure, and estimate trait heritability. However, estimation of kinship is challenging for spar...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007021
更新日期:2017-09-29 00:00:00
abstract::Through as yet undefined proteins and pathways, the SUMO-targeted ubiquitin ligase (STUbL) suppresses genomic instability by ubiquitinating SUMO conjugated proteins and driving their proteasomal destruction. Here, we identify a critical function for fission yeast STUbL in suppressing spontaneous and chemically induced...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001320
更新日期:2011-03-01 00:00:00
abstract::In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004829
更新日期:2014-12-04 00:00:00
abstract::In Drosophila, 50 classes of olfactory receptor neurons (ORNs) connect to 50 class-specific and uniquely positioned glomeruli in the antennal lobe. Despite the identification of cell surface receptors regulating axon guidance, how ORN axons sort to form 50 stereotypical glomeruli remains unclear. Here we show that the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007560
更新日期:2018-08-13 00:00:00
abstract::Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004713
更新日期:2014-11-06 00:00:00
abstract::Transcript elongation by RNA polymerase II (RNAPII) is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1) plays a key role in coord...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002822
更新日期:2012-01-01 00:00:00
abstract::During development of the cerebral cortex, neural stem cells (NSCs) divide symmetrically to proliferate and asymmetrically to generate neurons. Although faithful segregation of mitotic chromosomes is critical for NSC divisions, its fundamental mechanism remains unclear. A class of evolutionarily conserved protein comp...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004847
更新日期:2014-12-04 00:00:00
abstract::Complex trait genome-wide association studies (GWAS) provide an efficient strategy for evaluating large numbers of common variants in large numbers of individuals and for identifying trait-associated variants. Nevertheless, GWAS often leave much of the trait heritability unexplained. We hypothesized that some of this ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002198
更新日期:2011-07-01 00:00:00
abstract::AMP-activated protein kinase (AMPK) is an evolutionarily conserved master regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy sensor, AMPK activity is responsive to both metabolic inputs, for instance the ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two genes, a...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004394
更新日期:2014-06-12 00:00:00
abstract::Bacteria encode a single-stranded DNA (ssDNA) binding protein (SSB) crucial for genome maintenance. In Bacillus subtilis and Streptococcus pneumoniae, an alternative SSB, SsbB, is expressed uniquely during competence for genetic transformation, but its precise role has been disappointingly obscure. Here, we report our...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002156
更新日期:2011-06-01 00:00:00
abstract::The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter the cell cycle and divide to replace damaged cells. This capability is substantially reduced upon chronic damage, but it is not clear if this is a cause or consequence of liver disease. Here, we investigate wh...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009084
更新日期:2020-11-04 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pgen.1005038.]. ...
journal_title:PLoS genetics
pub_type: 已发布勘误
doi:10.1371/journal.pgen.1006559
更新日期:2017-01-20 00:00:00
abstract::Heterozygous mutations in the PRPF31 gene cause autosomal dominant retinitis pigmentosa (adRP), a hereditary disorder leading to progressive blindness. In some cases, such mutations display incomplete penetrance, implying that certain carriers develop retinal degeneration while others have no symptoms at all. Asymptom...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003040
更新日期:2012-01-01 00:00:00
abstract::We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome-car...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000291
更新日期:2008-12-01 00:00:00
abstract::The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006372
更新日期:2016-10-14 00:00:00
abstract::Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000099
更新日期:2008-06-20 00:00:00
abstract::The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC) is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated wi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000429
更新日期:2009-03-01 00:00:00
abstract::Kidney function depends on the nephron, which comprises a blood filter, a tubule that is subdivided into functionally distinct segments, and a collecting duct. How these regions arise during development is poorly understood. The zebrafish pronephros consists of two linear nephrons that develop from the intermediate me...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030189
更新日期:2007-10-01 00:00:00
abstract::Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiate...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006080
更新日期:2016-05-23 00:00:00
abstract::Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To u...
journal_title:PLoS genetics
pub_type: 杂志文章,meta分析
doi:10.1371/journal.pgen.1003394
更新日期:2013-03-01 00:00:00
abstract::Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES) cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and ide...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030145
更新日期:2007-08-01 00:00:00
abstract::Sexual dimorphisms in trait expression are widespread among animals and are especially pronounced in ornaments and weapons of sexual selection, which can attain exaggerated sizes. Expression of exaggerated traits is usually male-specific and nutrition sensitive. Consequently, the developmental mechanisms generating se...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004098
更新日期:2014-01-01 00:00:00
abstract::Genome duplications are important evolutionary events that impact the rate and spectrum of beneficial mutations and thus the rate of adaptation. Laboratory evolution experiments initiated with haploid Saccharomyces cerevisiae cultures repeatedly experience whole-genome duplication (WGD). We report recurrent genome dup...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007396
更新日期:2018-05-25 00:00:00
abstract::SKN-1, the Caenorhabditis elegans Nrf1/2/3 ortholog, promotes both oxidative stress resistance and longevity. SKN-1 responds to oxidative stress by upregulating genes that detoxify and defend against free radicals and other reactive molecules, a SKN-1/Nrf function that is both well-known and conserved. Here we show th...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002119
更新日期:2011-06-01 00:00:00
abstract::Long interspersed nuclear element-1s (LINE-1s, or L1s) are an active family of retrotransposable elements that continue to mutate mammalian genomes. Despite the large contribution of L1 to mammalian genome evolution, we do not know where active L1 particles (particles in the process of retrotransposition) are located ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006837
更新日期:2017-06-06 00:00:00