Abstract:
:Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
journal_name
Naturejournal_title
Natureauthors
Joshi PK,Esko T,Mattsson H,Eklund N,Gandin I,Nutile T,Jackson AU,Schurmann C,Smith AV,Zhang W,Okada Y,Stančáková A,Faul JD,Zhao W,Bartz TM,Concas MP,Franceschini N,Enroth S,Vitart V,Trompet S,Guo X,Chasman DI,doi
10.1038/nature14618subject
Has Abstractpub_date
2015-07-23 00:00:00pages
459-462issue
7561eissn
0028-0836issn
1476-4687journal_volume
523pub_type
杂志文章,meta分析相关文献
NATURE文献大全abstract::Magnetars are neutron stars with X-ray and soft γ-ray outbursts thought to be powered by intense internal magnetic fields. Like conventional neutron stars in the form of radio pulsars, magnetars exhibit 'glitches' during which angular momentum is believed to be transferred between the solid outer crust and the superfl...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12159
更新日期:2013-05-30 00:00:00
abstract::Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and ce...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2032-3
更新日期:2020-02-01 00:00:00
abstract::The importance of the dopaminergic system in brain function has been emphasized by its association with neurological and psychiatric disorders such as Parkinson's disease and schizophrenia. On the basis of their biochemical and pharmacological characteristics, dopamine receptors are classified into D1 and D2 subtypes....
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/347076a0
更新日期:1990-09-06 00:00:00
abstract::Recent work demonstrates that stochastic fluctuations in molecular populations have consequences for gene regulation. Previous experiments focused on noise sources or noise propagation through gene networks by measuring noise magnitudes. However, in theoretical analysis, we showed that noise frequency content is deter...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04194
更新日期:2006-02-02 00:00:00
abstract::Multiplicative operations are important in sensory processing, but their biophysical implementation remains largely unknown. We investigated an identified neuron (the lobula giant movement detector, LGMD, of locusts) whose output firing rate in response to looming visual stimuli has been described by two models, one o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01190
更新日期:2002-11-21 00:00:00
abstract::Viruses are the most abundant biological organisms of the world's oceans. Viral infections are a substantial source of mortality in a range of organisms-including autotrophic and heterotrophic plankton-but their impact on the deep ocean and benthic biosphere is completely unknown. Here we report that viral production ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07268
更新日期:2008-08-28 00:00:00
abstract::Chick embryo fibroblasts (CEF) infected with avian sarcoma virus become rapidly transformed as a result of expression of the viral src gene in the form of a single polypeptide of molecular weight 60,000 (pp60src) with protein kinase activity and suggested preferential association with the plasma membrane. Studies with...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/287241a0
更新日期:1980-09-18 00:00:00
abstract::In Fig. 3d this Letter, the R2 value should have been '0.19' instead of '0.66'; this has been corrected online. ...
journal_title:Nature
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41586-019-0893-0
更新日期:2019-02-01 00:00:00
abstract::Seismological observations have revealed the existence of low-velocity and high-attenuation zones above the discontinuity at 410 km depth, at the base of the Earth's upper mantle. It has been suggested that a small amount of melt could be responsible for such anomalies. The density of silicate melt under dry condition...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04352
更新日期:2006-01-12 00:00:00
abstract::Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of h...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10369
更新日期:2011-09-18 00:00:00
abstract::Angiotensin II is an important effector molecule controlling blood pressure and volume in the cardiovascular system. Its importance is manifested by the efficacy of angiotensin-converting enzyme inhibitors in the treatment of hypertension and congestive heart failure. Angiotensin II interacts with two pharmacologicall...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/351233a0
更新日期:1991-05-16 00:00:00
abstract::Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We des...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05453
更新日期:2007-01-11 00:00:00
abstract::Phase-dependent forms of microscopy (such as phase contrast, interference, or polarization microscopy) have been used for many years; the amount of phase retardation produces images based mainly on index of refraction. We have developed a microscope that forms images that depend on small differences in extinction for ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/328452a0
更新日期:1987-07-30 00:00:00
abstract::The T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR alpha and beta chains. Selection is based on the recognition by newly emergent T cells of self-ligands associated with molecules of the major histocompatibility complex: some combinations result in positive selecti...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/349531a0
更新日期:1991-02-07 00:00:00
abstract::Apart from the retroviral gag, pol and env the HIV genome contains the F (3' orf) gene which encodes a polypeptide of 206 amino acids which is myristylated at the N-terminal and whose function is unknown. We have expressed the F gene in Escherichia coli and from a recombinant vaccinia virus, VVTGfHIV. The F-protein pr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/330266a0
更新日期:1987-11-19 00:00:00
abstract::The assembly of ribosomes in bacterial cells is a complex process that remains poorly characterized. The in vitro assembly of active ribosomal subunits from purified RNA and protein components indicates that all of the information for proper assembly resides in the primary sequences of these macromolecules. On the oth...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/336496a0
更新日期:1988-12-01 00:00:00
abstract::The hot streak-loosely defined as 'winning begets more winnings'-highlights a specific period during which an individual's performance is substantially better than his or her typical performance. Although hot streaks have been widely debated in sports1,2, gambling3-5 and financial markets6,7 over the past several deca...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0315-8
更新日期:2018-07-01 00:00:00
abstract::Growth factors raise intracellular pH (pHi) by stimulating Na+/H+ exchange in the absence of HCO3-. In mutant cells that lack the Na+/H+ exchange activity, this alkalinization does not occur, and the cells do not proliferate without artificial elevation of pHi. It has therefore been widely suggested that an early pHi ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/337648a0
更新日期:1989-02-16 00:00:00
abstract::Muscarinic receptors of cardiac pacemaker and atrial cells are linked to a potassium channel (IK.ACh) by a pertussis toxin-sensitive GTP-binding protein. The dissociation of G-proteins leads to the generation of two potential transducing elements, alpha-GTP and beta gamma. IK.ACh is activated by G-protein alpha- and b...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/337557a0
更新日期:1989-02-09 00:00:00
abstract::Large, actively swimming suspension feeders evolved several times in Earth's history, arising independently from groups as diverse as sharks, rays and stem teleost fishes, and in mysticete whales. However, animals occupying this niche have not been identified from the early Palaeozoic era. Anomalocarids, a group of st...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13010
更新日期:2014-03-27 00:00:00
abstract::The four R-spondin secreted ligands (RSPO1-RSPO4) act via their cognate LGR4, LGR5 and LGR6 receptors to amplify WNT signalling1-3. Here we report an allelic series of recessive RSPO2 mutations in humans that cause tetra-amelia syndrome, which is characterized by lung aplasia and a total absence of the four limbs. Fun...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0118-y
更新日期:2018-05-01 00:00:00
abstract::Genomic imprinting is an allele-specific gene expression system that is important for mammalian development and function. The molecular basis of genomic imprinting is allele-specific DNA methylation. Although it is well known that the de novo DNA methyltransferases Dnmt3a and Dnmt3b are responsible for the establishme...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12805
更新日期:2013-12-19 00:00:00
abstract::Online hate and extremist narratives have been linked to abhorrent real-world events, including a current surge in hate crimes1-6 and an alarming increase in youth suicides that result from social media vitriol7; inciting mass shootings such as the 2019 attack in Christchurch, stabbings and bombings8-11; recruitment o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1494-7
更新日期:2019-09-01 00:00:00
abstract::For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules. However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Eme...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07882
更新日期:2009-03-19 00:00:00
abstract::Human T-cell leukaemia virus (HTLV), first isolated in the United States from a patient with cutaneous T-cell lymphoma, is a unique horizontally transmitted retrovirus which is highly associated with certain adult T-cell malignancies. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. In the accompany...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/305060a0
更新日期:1983-09-01 00:00:00
abstract::It is generally accepted that the specific function of a gene depends on its coding sequence. The three paired-box and homeobox genes paired (prd), gooseberry (gsb) and gooseberry neuro (gsbn) have distinct developmental functions in Drosophila embryogenesis. During the syncytial blastoderm stage, the pair-rule gene p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/367083a0
更新日期:1994-01-06 00:00:00
abstract::The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nati...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature11148
更新日期:2012-06-06 00:00:00
abstract::Mating and egg laying are tightly cooordinated events in the reproductive life of all oviparous females. Oviposition is typically rare in virgin females but is initiated after copulation. Here we identify the neural circuitry that links egg laying to mating status in Drosophila melanogaster. Activation of female-speci...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2055-9
更新日期:2020-03-01 00:00:00
abstract::Warming surface temperatures have driven a substantial reduction in the extent and duration of Northern Hemisphere snow cover1-3. These changes in snow cover affect Earth's climate system via the surface energy budget, and influence freshwater resources across a large proportion of the Northern Hemisphere4-6. In contr...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/s41586-020-2258-0
更新日期:2020-05-01 00:00:00
abstract::Fluctuations in the counting rate of photons originating from uncorrelated point sources become, within the coherently illuminated area, slightly enhanced compared to a random sequence of classical particles. This phenomenon, known in astronomy as the Hanbury Brown-Twiss effect, is a consequence of quantum interferenc...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature00911
更新日期:2002-07-25 00:00:00