ライフサイエンスコーパス: pleiotropy

1 re independent of calcium levels (horizontal pleiotropy).

2 or reproduction later in life (antagonistic pleiotropy).

3 een otherwise independent traits (horizontal pleiotropy).

4 l mutations affecting multiple traits (i.e., pleiotropy).

5 rrelate no matter the perturbation (vertical pleiotropy).

6 nce alternative disease-pathways (horizontal pleiotropy).

7 st that this result was biased by horizontal pleiotropy.

8 ful strategy to decouple cytokine functional pleiotropy.

9 re that exists between diagnoses, genes, and pleiotropy.

10 y analyses supporting a substantial role for pleiotropy.

11 pathways, tissues, gene ontology and genetic pleiotropy.

12 : the important role and pervasive nature of pleiotropy.

13 evels but indicated the existence of genetic pleiotropy.

14 instances of both agonistic and antagonistic pleiotropy.

15 ypes, potentially accounting for the genetic pleiotropy.

16 erent functional strategies that underpin TH pleiotropy.

17 imit both known and unknown forms of genetic pleiotropy.

18 henotype relationships resembling widespread pleiotropy.

19 s and what is the mechanistic basis for this pleiotropy.

20 ovide insights into gene regulation and PMM2 pleiotropy.

21 reliably separate causality from horizontal pleiotropy.

22 ysis of multiple GWAS datasets by leveraging pleiotropy.

23 mplex traits share common risk basis, namely pleiotropy.

24 one gene might be associated with phenotypic pleiotropy.

25 cular and nonvascular risk factors to assess pleiotropy.

26 these estimates might be inflated by hidden pleiotropy.

27 e of the important clinical repercussions of pleiotropy.

28 ple evidence of both vertical and horizontal pleiotropy.

29 s are maintained as a result of antagonistic pleiotropy.

30 or variation in the magnitude of deleterious pleiotropy.

31 removed those SNPs with potential horizontal pleiotropy.

32 have led to pollinator-mediated deleterious pleiotropy.

33 sis to outnumber overdominant, and extensive pleiotropy.

34 penetrance and sex specificity resulting in pleiotropy.

35 te a causal effect accounting for unmeasured pleiotropy.

36 y analyses for population stratification and pleiotropy.

37 nes are phenodeviant, with 65% demonstrating pleiotropy.

38 marker except for uric acid, arguing against pleiotropy.

39 tive trait loci [QTL]) acting via horizontal pleiotropy.

40 that the observations are not due to genetic pleiotropy.

41 end to act very specifically, indicating low pleiotropy.

42 gs and confers risk for MCM through vertical pleiotropy.

43 ytosol, which can account for the phenotypic pleiotropy.

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

45 aging in line with the theory of antagonist pleiotropy.

46 ul in the clinic because of their functional pleiotropy.

47 er estimates may be biased due to horizontal pleiotropy.

48 oaches, and can directly test for horizontal pleiotropy.

49 s controlled by loci with varying degrees of pleiotropy.

50 ll 33, 729-740 (1983)], might be affected by pleiotropy.

51 ding of these genetic analyses by horizontal pleiotropy.

52 prove the power of gene discovery and reveal pleiotropy.

53 urvival of deleterious genes is antagonistic pleiotropy.

54 with blood lipids levels, selected to avoid pleiotropy.

55 c for KA; the 16p11.2 locus showed extensive pleiotropy.

56 93 (0.88; 0.98), respectively, indicating no pleiotropy.

57 ucture-based approach to decoupling IFNgamma pleiotropy.

58 n and multiple other renal traits indicating pleiotropy.

59 is, hypothesising they are due to horizontal pleiotropy.

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

61 omprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, populati

62 association studies (GWASs) reveal pervasive pleiotropy across a wide variety of phenotypes.

63 ons in human genetics, such as the extent of pleiotropy across the genome and variation in genetic ar

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

65 l heterogeneity (primarily due to horizontal pleiotropy, addressing a major challenge of transcriptom

66 , we did detect a potential case of adaptive pleiotropy among floral size and nectar traits.

67 21 [1.04-1.42]; p=0.016), although potential pleiotropy among genetic variants used as instruments fo

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

69 germline and soma, relevant to antagonistic pleiotropy, an evolutionary process underlying ageing an

70 tly, we evaluated the presence of horizontal pleiotropy and assessed whether there is any evidence fo

71 etween the dementias, genetic heterogeneity, pleiotropy and concurrent mutations.

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

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

74 We tested for pleiotropy and enrichment of functional loci between bir

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

76 way and that, more broadly, they show strong pleiotropy and epistasis.

77 ications will need to account for unexpected pleiotropy and evolutionary context.

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

79 traits, we provide an extensive overview of pleiotropy and genetic architecture.

80 levels and advances our understanding of the pleiotropy and genetic co-architecture between brain vol

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

82 leterious soon after because of antagonistic pleiotropy and hindering their fixations relative to syn

83 often these relationships underlie vertical pleiotropy and how often these relationships are modifie

84 noncoding localization, as well as pervasive pleiotropy and incomplete penetrance.

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

86 emission, potentially reflecting the limited pleiotropy and large effect of its inactivation.

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

88 Our findings demonstrate widespread pleiotropy and offer further insight into the complex ge

89 ed and tested for the confounding effects of pleiotropy and population stratification on our analysis

90 ry architecture of optix is characterized by pleiotropy and regulatory fragility, where deletion of i

91 Genetic pleiotropy and sample heterogeneity suggest that very la

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

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

94 however, the possible existence of residual pleiotropy and stratification remains a limitation of th

95 nd de novo mutations; shown how antagonistic pleiotropy and temporally varying selection maintain pol

96 Challenges such as pleiotropy and the non-specificity of molQTLs remain, an

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

98 Presence of pleiotropy and the robustness of the results were assess

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

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

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

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

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

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

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

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

107 y bind diverse partners, display significant pleiotropy, and connect many cellular systems.

108 gene on trait in the presence of horizontal pleiotropy, and is scalable to hundreds of thousands of

109 N package that simulates pleiotropy, partial pleiotropy, and spurious pleiotropy in a wide range of g

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

111 different assumptions about the presence of pleiotropy, and when accounting for the effects of tradi

112 adaptation, a relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since

113 trade-offs, a concept known as antagonistic pleiotropy (AP).

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

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

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

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

118 MR) analysis, variants that exert horizontal pleiotropy are typically treated as a nuisance.

119 is study thus reveals the molecular basis of pleiotropy associated with plant productivity, adaptabil

120 remendous locus heterogeneity and functional pleiotropy associated with the more than 100 identified

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

122 Here we report how the 'no horizontal pleiotropy assumption' is strengthened when proteins are

123 iew, we summarize evidence in psychiatry for pleiotropy at multiple levels of analysis: from overall

124 ted with ADHD and ASD, respectively, through pleiotropy at shared genetic variants.

125 loped to enhance exploration of phenome-wide pleiotropy at the genome-wide level through the efficien

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

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

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

129 n several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy indiv

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

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

132 is identified a complex pattern of polygenic pleiotropy between CC and other immune-mediated diseases

133 Pleiotropy between cognitive and health traits was quant

134 Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepilep

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

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

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

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

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

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

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

142 a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

143 This implies the pleiotropy between years of schooling and schizophrenia

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

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

146 nging dependencies suggest a nuanced view of pleiotropy: biological systems demonstrate limited pleio

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

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

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

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

151 ynergistic, frequency-dependent cooperation, pleiotropy can raise the frequency up to a point where c

152 phenotypes, especially those resulting from pleiotropy, can constrain or facilitate trait evolution.

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

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

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

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

157 ce to date for a gene having an antagonistic pleiotropy effect on human cognitive function across a w

158 The pleiotropy exhibited between cognitive function and psyc

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

160 The remarkable extent of pleiotropy exhibited by SLC39A8 A391T raises key questio

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

162 , as well as little evidence of antagonistic pleiotropy (few trait correlations and QTL colocalizatio

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

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

165 Our method suggests that exploiting pleiotropy for applications in evolutionary medicine wou

166 We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that conver

167 e with an exploration of the implications of pleiotropy for understanding the genetic basis of psychi

168 classic genetic explanation is antagonistic pleiotropy: genes underlying the generalism produce 'jac

169 There was little evidence to imply that pleiotropy had biased results.

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

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

172 Bias due to horizontal pleiotropy, however, remains a major concern.

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

174 variants for these disorders had evidence of pleiotropy (i.e., impact on multiple psychiatric disorde

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

176 Investigations of pleiotropy identify 12 cancer pairs exhibiting either po

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

178 pleiotropy, partial pleiotropy, and spurious pleiotropy in a wide range of genetic architectures, inc

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

180 ropy: biological systems demonstrate limited pleiotropy in any given context, but across contexts (e.

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

182 all, our findings revealed pervasive genetic pleiotropy in early growth and adulthood cardiometabolic

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

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

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

186 Pleiotropy in sub-surface GWAS significance strata can b

187 in adulthood; however, the extent of genetic pleiotropy in the association has not been comprehensive

188 We assessed the role of pleiotropy in the differentiation of floral and other re

189 evidence supporting a model of antagonistic pleiotropy in the DNA damage response where histone degr

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

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

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

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

194 -44 may represent an example of antagonistic pleiotropy, in which low-expression level in young anima

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

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

197 We examine underlying mechanisms of observed pleiotropy, including genetic effects on neurodevelopmen

198 ypes, reflecting genetic phenomena including pleiotropy, incomplete penetrance and variable expressiv

199 (Disease Specificity Index) and DPI (Disease Pleiotropy Index).

200 The finding of genetic pleiotropy indicates the existence of common upstream pa

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

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

203 l loci associated with CAD and BP, a genetic-pleiotropy-informed conditional false discovery rate (cF

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

205 d, there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex disease

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

207 Pleiotropy is also critical to initiatives in evolutiona

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

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

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

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 Horizontal pleiotropy is pervasive throughout the human genome, pro

214 ating that positive rather than antagonistic pleiotropy is pervasive.

215 Indeed, pleiotropy is proposed as a main driver of repeated conv

216 Pleiotropy is the well-established phenomenon of a singl

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

218 types; however, the late timing reduces this pleiotropy, making Hox genes suitable targets.

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 growth in non-smokers suggests that genetic pleiotropy may have masked a stronger association in smo

222 on that avoid or compensate for antagonistic pleiotropy may limit access to certain future evolutiona

223 Alternatively, pleiotropy may result from genetic changes that impose c

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

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

226 We develop a multi-trait pleiotropy model of the heterogeneity in the exposure-ou

227 stations, consistent with a neuropsychiatric pleiotropy model.

228 Pleiotropy occurs when one gene influences more than one

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

230 Here, we review examples of pleiotropy of flowering-time genes and highlight those t

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

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

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

234 care systems to evaluate the penetrance and pleiotropy of genetic risk for schizophrenia.

235 , the latter appear to result from pervasive pleiotropy of height-associated genes.

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

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

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

239 s assessed the potential impact of bias from pleiotropy on estimates.

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

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

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

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

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

245 We found significantly abundant genetic pleiotropy (P < 3.3 x 10(-3)) and enrichment of function

246 PHENOTYPES, an R/CRAN package that simulates pleiotropy, partial pleiotropy, and spurious pleiotropy

247 thesize that the limited availability of low-pleiotropy paths predetermines closely related species t

248 cle may mitigate evolutionary constraints of pleiotropy, permitting traits to respond more independen

249 Pleiotropy plays a central role in debates about how com

250 Pleiotropy plays an important role in furthering our und

251 esults highlight the central role horizontal pleiotropy plays in the genetic architecture of human ph

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

253 nefit from understanding the extent to which pleiotropy reflects inherent relationships among phenoty

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

255 MR-Egger, MR pleiotropy residual sum and outlier, weighted median, an

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

257 3.1x10(-3) for replication, P<2.0x10(-4) for pleiotropy): Seven of these were specific to European Am

258 Investigation of pleiotropy showed large overlaps in genetic variants wit

259 in specifying plant phenotypes generally or pleiotropy specifically.

260 modating different assumptions about genetic pleiotropy strengthened causal inference.

261 the derived activity are still unknown, such pleiotropy suggests that enhancer accessibility could be

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

263 e positives induced by correlated horizontal pleiotropy than other methods.

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

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

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

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

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

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

270 o the organisms that bear them, antagonistic pleiotropy, the importance of pre-existing genetic varia

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

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

273 as explained by amelioration of antagonistic pleiotropy through epistasis(13,14,20-22).

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

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

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

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

278 R-TRYX, a framework that exploits horizontal pleiotropy to discover putative risk factors for disease

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

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

281 We identified pleiotropy, transcriptional signatures of perturbations,

282 We develop a method to quantify horizontal pleiotropy using genome-wide association summary statist

283 Genetic pleiotropy was also estimated.

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

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

286 Complex pleiotropy was supported when contrasting multidisease s

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

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

289 hat no instrument outliers and no horizontal pleiotropy were likely to bias the results.

290 Pleiotropy-when a single mutation affects multiple trait

291 Antagonist pleiotropy, where a gene exerts a beneficial effect at e

292 Horizontal pleiotropy, where one variant has independent effects on

293 Correlated horizontal pleiotropy, which arises when variants affect both trait

294 orms of stable cooperation can evolve though pleiotropy with a beneficial private trait.

295 brain WM tracts and provides the overview of pleiotropy with cognitive and mental health traits.

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

300 tion in behavior, plasticity, and behavioral pleiotropy, with special attention to recent findings on