ライフサイエンスコーパス: pleiotropy

1 or reproduction later in life (antagonistic pleiotropy).

2 influenced by common genetic factors (e.g., pleiotropy).

3 y analyses for population stratification and pleiotropy.

4 nes are phenodeviant, with 65% demonstrating pleiotropy.

5 marker except for uric acid, arguing against pleiotropy.

6 that the observations are not due to genetic pleiotropy.

7 end to act very specifically, indicating low pleiotropy.

8 ytosol, which can account for the phenotypic pleiotropy.

9 an array of functions, a phenomenon known as pleiotropy.

10 imit both known and unknown forms of genetic pleiotropy.

11 aging in line with the theory of antagonist pleiotropy.

12 ul in the clinic because of their functional pleiotropy.

13 om disparate meanings and interpretations of pleiotropy.

14 tal questions about the nature and extent of pleiotropy.

15 ke evolutionary paths that minimize negative pleiotropy.

16 FTD-associated genes may contribute to this pleiotropy.

17 ation is due primarily to linkage and not to pleiotropy.

18 us evidence that the association arises from pleiotropy.

19 genomic regions with statistical evidence of pleiotropy.

20 ttle epistasis, environmental interaction or pleiotropy.

21 ess fundamental issues such as epistasis and pleiotropy.

22 ts, we here describe the genomic patterns of pleiotropy.

23 53 pathway as a good example of antagonistic pleiotropy.

24 l mechanistic basis for this relationship is pleiotropy.

25 ributes to MPN predisposition and phenotypic pleiotropy.

26 ld be explained in all cases by antagonistic pleiotropy.

27 on or gene manipulation experiments focus on pleiotropy.

28 in other environments, we have antagonistic pleiotropy.

29 henotype relationships resembling widespread pleiotropy.

30 e size of the effects does not decrease with pleiotropy.

31 orally limited - a phenomenon termed limited pleiotropy.

32 protein connectivity correlates with genetic pleiotropy.

33 This phenomenon is known as pleiotropy.

34 a loss-of-function mutation with restricted pleiotropy.

35 ified QTL, to test coincident linkage versus pleiotropy.

36 the traits is attributed to tight linkage or pleiotropy.

37 ovide insights into gene regulation and PMM2 pleiotropy.

38 reliably separate causality from horizontal pleiotropy.

39 ysis of multiple GWAS datasets by leveraging pleiotropy.

40 instances of both agonistic and antagonistic pleiotropy.

41 mplex traits share common risk basis, namely pleiotropy.

42 one gene might be associated with phenotypic pleiotropy.

43 ypes, potentially accounting for the genetic pleiotropy.

44 cular and nonvascular risk factors to assess pleiotropy.

45 these estimates might be inflated by hidden pleiotropy.

46 e of the important clinical repercussions of pleiotropy.

47 s are maintained as a result of antagonistic pleiotropy.

48 or variation in the magnitude of deleterious pleiotropy.

49 erent functional strategies that underpin TH pleiotropy.

50 have led to pollinator-mediated deleterious pleiotropy.

51 sis to outnumber overdominant, and extensive pleiotropy.

52 penetrance and sex specificity resulting in pleiotropy.

53 te a causal effect accounting for unmeasured pleiotropy.

54 mpeting biological functions (i.e., hormonal pleiotropy) [1].

55 We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pl

56 Pleiotropy across the 8q24 region is perhaps the most in

57 results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent n

58 they are linked through broad epistasis and pleiotropy affecting a reproductive regulatory network t

59 In bacteria, they exhibit a high degree of pleiotropy, affecting both individual and multicellular

60 covariation of these traits is likely due to pleiotropy, although physically linked loci that indepen

61 cycumulation (MA) lines show any evidence of pleiotropy among accumulated mutations and find that, fo

62 y one fitness component do show evidence for pleiotropy among accumulated mutations.

63 identify susceptibility loci and investigate pleiotropy among genetic variants using a subset-based m

64 We present a systematic review of pleiotropy among SNPs and genes reported to show genome-

65 of previously undetected novel developmental pleiotropy among these elements.

66 lse discovery rate (FDR) to evaluate genetic pleiotropy and conditional FDR to identify novel FTD-ass

67 tly proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any cli

68 Our findings provide evidence that pleiotropy and epistasis are important factors in the ge

69 eractions, multiple deviations are caused by pleiotropy and epistasis in metabolism.

70 lications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer

71 in a way that points to extensive biological pleiotropy and further challenges the biological validit

72 Both antagonistic pleiotropy and genetic variation in the rate of senescen

73 ing for smoking behavior, indicating genetic pleiotropy and independent model.

74 ed the potential importance of the epistatic pleiotropy and of the impact of host living conditions.

75 Genetic pleiotropy and sample heterogeneity suggest that very la

76 se naturally in situations with antagonistic pleiotropy and seasonal changes in the relative importan

77 s as a complex trait that exhibits extensive pleiotropy and sex specificity.

78 that they are most likely associated due to pleiotropy and shared biological basis, thus providing o

79 ate major revisions of theoretical models of pleiotropy and suggest that pleiotropy has not only allo

80 ngitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically

81 s an Empirical Bayes approach to integrating Pleiotropy and Tissue-Specific information (EPS) for pri

82 EPS enables rigorous hypothesis testing of pleiotropy and tissue-specific risk gene expression patt

83 yses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathwa

84 ther of which results from cytokine receptor pleiotropy and/or undesired activation of off-target cel

85 This review traces the history of the term "pleiotropy" and reevaluates its current place in the fie

86 ts for association with multiple phenotypes (pleiotropy) and for testing multiple variants for associ

87 risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants

88 warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SN

89 n arise in several ways including mediation, pleiotropy, and confounding, and several examples of gen

90 and we discuss the importance of epistasis, pleiotropy, and gene by environment interactions.

91 estimates to be obtained of the magnitude of pleiotropy, and in reviews of such data others have conc

92 tional hypothesis tests for QTL main effect, pleiotropy, and QTL-by-environment interaction in multip

93 wever, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete

94 sults demonstrate that both adaptability and pleiotropy are complex traits, with extensive heritable

95 ogic model is offered in which 3 patterns of pleiotropy are hypothesized to be the principal modes of

96 Understanding gene interaction and pleiotropy are long-standing goals of developmental and

97 onclusions on limits to evolvability through pleiotropy are not robust.

98 ltivariate association methods that consider pleiotropy are often more powerful than univariate metho

99 terogeneity, variable penetrance and genetic pleiotropy are pervasive characteristics of autism genet

100 ggest that certain regulatory genes with low pleiotropy are predisposed to readily integrate into or

101 etic correlations among traits (often due to pleiotropy) are such that successful or rapid dispersers

102 his haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 di

103 levels and apoptosis exhibited antagonistic pleiotropy associated with mitochondrial defects.

104 This scaling property counteracts the pleiotropy-associated reduction in adaptation rate (i.e.

105 influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampli

106 software aimed at visualizing and evaluating pleiotropy at a regional level.

107 AAs and identified allelic heterogeneity and pleiotropy at several previously known genetic loci asso

108 Evidence of directional pleiotropy averaged across all variants was sought using

109 ow-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white b

110 proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in ad

111 variate and bivariate linkage to investigate pleiotropy between amygdala volume and emotion recogniti

112 al and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS.

113 Also noted was evidence of genome-level pleiotropy between CAD and major depressive disorder and

114 Pleiotropy between cognitive and health traits was quant

115 provide insight into the molecular basis of pleiotropy between complex traits.

116 NPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk

117 Empirical data showed the genetic pleiotropy between nicotine dependence and COPD or lung

118 s provide the first systematic evaluation of pleiotropy between OA and BMD, highlight genes with biol

119 opean ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease

120 n between phenotypes subject to antagonistic pleiotropy between reproductive effort and mortality rat

121 d together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC s

122 To date, the genetic pleiotropy between smoking behavior and lung function/ch

123 ve memory, and intelligence, no evidence for pleiotropy between these classes of phenotypes was obser

124 Therefore, pleiotropy between these major life stages likely influe

125 factors for metabolic diseases substantiated pleiotropy between traits.

126 ) evidence for common genetic underpinnings (pleiotropy) between AUD risk and subcortical volumes.

127 factors, the estimated genetic correlation (pleiotropy) between baseline CAC quantity and CAC progre

128 se results in trade-offs (i.e., antagonistic pleiotropy) between host MHC genotypes; both viral fitne

129 ity analysis provided evidence of horizontal pleiotropy bias (p = 0.04) diluting the estimates toward

130 e also highlighting new aspects of metabolic pleiotropy both in terms of the breadth of loci altering

131 n randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests ther

132 ther evidence that association is not due to pleiotropy by showing null effects in male non-drinkers,

133 mputational artifact; and respect biological pleiotropy, by which a term in the hierarchy can relate

134 Some authors have suggested that pleiotropy can impede evolutionary progress (a so-called

135 ft, leptokurtosis of mutational effects, and pleiotropy can increase the mean-optimum deviation great

136 Exploring genetic pleiotropy can provide clues to a mechanism underlying t

137 Pleiotropy can suggest either redundant phenotype measur

138 rly be the result of many factors, including pleiotropy, canalization and genetic redundancy.

139 Here, we describe distinct uses of the pleiotropy concept and explain the pitfalls associated w

140 In striking contrast to the developmental pleiotropy conferred by mutation in other plant Paf1C co

141 eles could be identified, or if antagonistic pleiotropy could be broken, the effects of aging might b

142 The possibility of genetic pleiotropy could not be discounted completely; however,

143 usibility of various phenomena attributed to pleiotropy depends on how many traits are affected by ea

144 th autosomal dominant inheritance often show pleiotropy, different degrees of penetrance, and variabl

145 x differences in associations which suggests pleiotropy does not underlie the associations, 3) provid

146 , including ploidy, dominance, heritability, pleiotropy, epistasis, mutational load and recombination

147 The pleiotropy exhibited between cognitive function and psyc

148 or specificities lead to the conclusion that pleiotropy exhibited by peptide genes influences ligand-

149 indings indicate that a substantial level of pleiotropy exists between cognitive abilities and many h

150 risk and lung function; and (2) the genetic pleiotropy follow causal or independent model.

151 We find additional evidence of pleiotropy for APOE, TOMM40, TCF7L2, and CETP variants,

152 In addition, the observation of extensive pleiotropy for some genes and singular associations for

153 ve implications concerning the importance of pleiotropy for the biological actions of miRNAs and prov

154 nd have implications about the importance of pleiotropy for the biological actions of miRNAs.

155 win studies demonstrated genetic covariance (pleiotropy) for the isoprostane and CHGB traits (rho(G)

156 first time we can empirically evaluate gene pleiotropy from the protein sequence analysis.

157 d shared genetic determination among traits (pleiotropy, genetic covariance, rho(G)) were estimated b

158 erall, models ignoring hidden confounding or pleiotropy had significantly poorer DIC scores.

159 Due to its central importance, pleiotropy has also been extensively modeled, albeit wit

160 nize the difference between modular and gene pleiotropy has confounded our understanding of the genet

161 Pleiotropy has had an important influence on the fields

162 contradicting the hypothesis of antagonistic pleiotropy has highlighted the importance of other facto

163 etical models of pleiotropy and suggest that pleiotropy has not only allowed but also promoted the ev

164 Different approaches to the study of pleiotropy have led to incongruence in the way that it i

165 Genetically, colobomata demonstrate pleiotropy, heterogeneity, variable expressivity, and re

166 the genome-wide observations of overall low pleiotropy, high modularity, and larger per-trait effect

167 ere we show that, compared with genes of low pleiotropy, highly pleiotropic genes participate in more

168 In support of this "hormonal pleiotropy" hypothesis, we find that in the common wasp,

169 ng number of reports suggest the ubiquity of pleiotropy, i.e. many complex phenotypes sharing common

170 This degree of pleiotropy implies that perturbations of these signaling

171 However, antagonistic pleiotropy imposed a cost during the adaptation to persi

172 u may reflect selection to minimize negative pleiotropy in a complex biosynthetic pathway.

173 Further evidence for pleiotropy in academic achievement was found using a met

174 ent limb variation via reductions to genetic pleiotropy in an ape-like last common ancestor (LCA).

175 In this Review, we discuss the evidence for pleiotropy in contemporary genetic mapping studies, new

176 vidence suggesting the existence of positive pleiotropy in cowpea based on positively correlated mean

177 deleterious pleiotropy, supporting a role of pleiotropy in determining the possible trajectories of a

178 This study examines the role of pleiotropy in explaining the link between cognitive func

179 hasize the importance of genetic linkage and pleiotropy in facilitating rapid divergence in sympatry.

180 Here we show, by studying pleiotropy in mice with the use of quantitative trait lo

181 ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in l

182 discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and mu

183 nsitivity analysis indicated no evidence for pleiotropy in the effect of schizophrenia on smoking ini

184 r genetic studies demonstrating considerable pleiotropy in the genetic architecture of these phenotyp

185 vernalization despite a lack of any obvious pleiotropy in the rvr1 mutant.

186 Our findings demonstrate genetic pleiotropy in these neurodegenerative diseases and indic

187 current state of knowledge of developmental pleiotropy in yeast and discuss its implications for und

188 -44 may represent an example of antagonistic pleiotropy, in which low-expression level in young anima

189 pistasis, meaning gene-gene interaction, and pleiotropy, in which one gene affects multiple phenotype

190 the reciprocal variance, suggesting genetic pleiotropy; in the best-fit model the polygenic score fo

191 e of shared risk alleles for complex traits (pleiotropy), including autoimmune and neuropsychiatric d

192 TH promoter haplotype 2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and

193 We use the term Pleiotropy Index to denote the number of traits with low

194 o derive the statistical distribution of the Pleiotropy Index under the null hypothesis of no genotyp

195 roximate the statistical significance of the Pleiotropy Index.

196 itivity analyses reduce the possibility that pleiotropy influenced our results, residual pleiotropy i

197 aking FLC a promising case for examining how pleiotropy influences adaptive evolution.

198 dies summary statistics and shared polygenic pleiotropy-informed conditional and conjunctional false

199 Given that limited pleiotropy is a common feature of cis-regulatory mutatio

200 Although pleiotropy is a common phenomenon with broad implication

201 late over time, but it is already clear that pleiotropy is a common property of genes and SNPs associ

202 pression changes across traits suggests that pleiotropy is a widespread phenomenon and points to spec

203 There is increasing evidence showing that pleiotropy is a widespread phenomenon in complex disease

204 Such pleiotropy is achieved via coordinate repression of a co

205 Gene pleiotropy is characterized by K distinct but correlated

206 om a range of model systems suggest that the pleiotropy is common among the loci responsible for flor

207 Pleiotropy is defined as the phenomenon in which a singl

208 otropy may have biased the results, residual pleiotropy is difficult to exclude entirely.

209 pleiotropy influenced our results, residual pleiotropy is difficult to exclude entirely.

210 ata others have concluded that the degree of pleiotropy is highly restricted, with implications on th

211 This genetic variation in adaptability and pleiotropy is largely determined by initial fitness, acc

212 the biological significance of epistasis and pleiotropy is often difficult.

213 ry outcomes, but distinguishing linkage from pleiotropy is often difficult.

214 One example of this pleiotropy is the Izh2p-dependent repression of FET3, a

215 Pleiotropy is the well-established phenomenon of a singl

216 e important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth f

217 We found little evidence for pleiotropy linking dyslipidemia and obesity to the other

218 These results suggest that the pleiotropy manifested by chromosomal parABS mutations co

219 pose that some Bardet-Biedl syndrome and MKS pleiotropy may be caused by mutations that impact TZP co

220 vity analyses decreased the possibility that pleiotropy may have biased the results, residual pleiotr

221 and human findings, we propose that genetic pleiotropy might partly explain the frequently observed

222 Deciphering the mechanisms underlying this pleiotropy might provide important information on the bi

223 These results suggest that antagonistic pleiotropy might underlie the occurrence of GA5 loss-of-

224 between components of fitness ("antagonistic pleiotropy")--might play an important role in maintainin

225 stations, consistent with a neuropsychiatric pleiotropy model.

226 arger per-trait effects from genes of higher pleiotropy necessitate major revisions of theoretical mo

227 nes by high relatedness, kin discrimination, pleiotropy, noble resistance, and lottery-like role assi

228 y influenced by population stratification or pleiotropy (odds ratio [OR] = 1.7, 95% CI: 1.3-2.2; p =

229 Because of the limited pleiotropy of cis-regulating mutations, the number of ci

230 report the genome-wide occurrence of limited pleiotropy of cis-regulatory mutations in barley (Hordeu

231 family of polypeptide cytokines exhibiting a pleiotropy of functions, from cell growth to angiogenesi

232 tes in the male germline, greater functional pleiotropy of genes expressed in females, and/or sexual

233 l conditions across life stages, and despite pleiotropy of genes that affect both flowering and germi

234 s using MR approaches that took into account pleiotropy of genetic instruments.

235 Moreover, the pleiotropy of HARP mutations is consistent with the func

236 ly cDNA microarrays to explore the potential pleiotropy of HMB-PP-activated Vgamma9/Vdelta2 T cells.

237 dings define HS as a mild PBD, expanding the pleiotropy of mutations in PEX1 and PEX6.

238 elop without Pax6 input and the considerable pleiotropy of Pax6 outside the visual system dictate fur

239 ence for an inverse relationship between the pleiotropy of SHOOTMERISTEMLESS (STM) and BREVIPEDICELLU

240 Such pleiotropy of SNORA42 suppression could be achieved at l

241 To investigate the pleiotropy of the glorund mutant phenotype, which includ

242 ion across the arthropods, and show that the pleiotropy of the Notch pathway can confound speculation

243 The level of pleiotropy of the SL-deficient ramosus1 (rms1) mutant is

244 on, we confirmed the genome-wide significant pleiotropy of these two regions based on the GWAS Catalo

245 The impact of pleiotropy on evolution has for decades been the subject

246 re be attributed to the result of biological pleiotropy or could be secondary to LOAD.

247 ll effect sizes with little-to-no detectable pleiotropy or epistasis.

248 a result of genetic colocalization either by pleiotropy or genetic linkage.

249 o sharing among all individuals (whole-group pleiotropy) or a subset of individuals in a genetically

250 ing on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CR

251 ch as functional constraints, epistasis, and pleiotropy play an important role in shaping the outcome

252 Pleiotropy prevents the use of the dormancy gene to impr

253 e diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of case

254 Pleiotropy refers to the phenomenon of a single mutation

255 tionary mechanism underlying this remarkable pleiotropy remains to be fully understood.

256 A loss-of-function studies is the biological pleiotropy resulting from multiple modes of action of si

257 e.g., NRG1 and ERBB4) displayed evidence for pleiotropy, revealing associations with four or more end

258 influenced by shared genetic determination (pleiotropy [rhoG]; for the CHGA precursor, rhoG=0.318+/-

259 This novel "pleiotropy scan" method may be useful for identifying su

260 3.1x10(-3) for replication, P<2.0x10(-4) for pleiotropy): Seven of these were specific to European Am

261 Investigation of pleiotropy showed large overlaps in genetic variants wit

262 In the presence of widespread pleiotropy, stabilizing selection on focal traits will a

263 Mutant studies are tallied for evidence of pleiotropy; studies of natural strains are analyzed with

264 or sex pheromones by escape from deleterious pleiotropy, supporting a role of pleiotropy in determini

265 Enhanced S-cone syndrome has more pleiotropy than previously appreciated.

266 we consider a biologically plausible form of pleiotropy that has hitherto been ignored in treatments

267 monstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an o

268 Antagonistic pleiotropy, that is, the negative fitness effect in the

269 Methods that embrace pleiotropy (the effect of one locus on more than one tra

270 rait variance accounted for by heredity) and pleiotropy (the genetic covariance or shared genetic det

271 lowest mortality rate and (via antagonistic pleiotropy) the lowest propagation rate qualified as evo

272 r any question about the nature or extent of pleiotropy, the appropriate answer is always 'What do yo

273 ne gene and minimize the potential impact of pleiotropy, the association was attenuated (OR 1.03, 95%

274 ses are interpreted as forms of antagonistic pleiotropy, the product of a "shortsighted watchmaker,"

275 The combination of polygenicity and gene pleiotropy-the influence of one gene on distinct phenoty

276 The antagonistic pleiotropy theory for the evolution of senescence predic

277 In the presence of pleiotropy, there exist risk loci that affect multiple p

278 at the trade-off is mediated by antagonistic pleiotropy through mutations that affect negative regula

279 This indicated the potential for pleiotropy to affect estimates and differences in perfor

280 The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matte

281 This motivated us to leverage pleiotropy to develop new statistical approaches to join

282 ated with BMD, highlighting the potential of pleiotropy to improve gene discovery.

283 e disequilibrium, genomic rearrangements and pleiotropy, to be tested.

284 We identified pleiotropy, transcriptional signatures of perturbations,

285 PAGE SNPs are also assessed for pleiotropy using the "phenome-wide association study" ap

286 Genetic pleiotropy was also estimated.

287 nlike several prior maize studies, extensive pleiotropy was found for C and N metabolites.

288 Significant evidence of pleiotropy was observed between PTSD and rheumatoid arth

289 The concept of pleiotropy was proposed a century ago, though up to now

290 Complex pleiotropy was supported when contrasting multidisease s

291 similar results, suggesting that directional pleiotropy was unlikely to be biasing the result (interc

292 To leverage pleiotropy, we introduce a low-rank structure to modulat

293 Haploinsufficiency and pleiotropy were both surprisingly common.

294 results from genetic tradeoffs (antagonistic pleiotropy), where native alleles are best adapted to lo

295 Examples of pleiotropy will accumulate over time, but it is already

296 genetic overlap and substantial evidence of pleiotropy with cognitive function and neuroticism.

297 Analyses of polygenic risk scores identified pleiotropy with neuropsychiatric traits and brain volume

298 Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related dis

299 ble, displaying joint genetic determination (pleiotropy) with autonomic activity and finally with blo

300 ations in the rpoB gene exhibit antagonistic pleiotropy, with fitness tradeoffs at 18 degrees C and f