ライフサイエンスコーパス: rare variant

1 tistically accurate methods to identify true rare variants.

2 tain significance, and 66 (17%) had multiple rare variants.

3 raditionally lacks the sensitivity to detect rare variants.

4 rtain significance, and 14 (4%) had multiple rare variants.

5 third of the 98 lipid loci tested, including rare variants.

6 of similar tests for gene-based analysis of rare variants.

7 iant and gene-based burden tests to identify rare variants.

8 identifies fine-scale genetic ancestry from rare variants.

9 ses, we performed an exome-based analysis of rare variants.

10 at a depth of coverage sufficient to detect rare variants.

11 erature on the phenotypes accompanying these rare variants.

12 resource to assess the clinical relevance of rare variants.

13 uencing, are often caused by high-penetrance rare variants.

14 combined effect of multiple low frequency or rare variants.

15 were associated with single sites and 7 with rare variants.

16 s heterogeneity and prevent the detection of rare variants.

17 also probed association in low-frequency and rare variants.

18 re tool MARV for Multi-phenotype Analysis of Rare Variants.

19 se studies are not practical for identifying rare variants.

20 Of the 27 rare variants, 22 were present in cases (18 missense, on

21 all accuracy and the quality of genotypes on rare variants, a new model calling procedure, named M-D,

22 ecture of AIS in which a polygenic burden of rare variants across extracellular matrix genes contribu

23 ogies can help researchers detect common and rare variants across the human genome in many individual

24 These two rare variants acted as gain-of-function mutations that i

25 C4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometri

26 For rare variant aggregate analysis, an exome-wide significa

27 l component analysis, and single variant and rare variant aggregate association analysis of >9 millio

28 alysis of a quantitative trait using several rare variant aggregate association methods.

29 t evidence for a replicable cardioprotective rare variant aggregation (P = 3.2 x 10(-31), n = 13 480)

30 There were 224 (59%) with >/=1 rare variant (allele frequency </=0.02%).

31 Detection of extremely rare variant alleles within a complex mixture of DNA mol

32 isms underlying NMDAR dysregulation by these rare variants allowed investigations of pharmacologic st

33 Together, our results indicate that rare variants alone or combined with common variants in

34 x 10(-9)) than observed in single phenotype rare variant analyses (P TG = 6.5 x 10(-8) and P FI = 0.

35 ociation studies, as well as copy number and rare variant analyses.

36 Likewise, rare variant analysis did not identify genes that reache

37 nalysis for common variants (MAF > 0.01) and rare variant analysis for low frequency and rare variant

38 ce of demography on genomic architecture and rare variant analysis in order to address inequalities i

39 se the HEALER framework to facilitate secure rare variants analysis with a small sample size.

40 ison with other commonly applied methods for rare variants analysis.

41 variant analysis, including single-phenotype rare variant and multi-phenotype common variant analysis

42 We identify a total of 79 genes with rare variants and 67 genes with common variants signific

43 sing interest to detect associations between rare variants and complex traits.

44 le-genome sequencing results to include only rare variants and conducted single variant tests, region

45 udies in MS will likely focus on the role of rare variants and endophenotypes.

46 racy compared with Phase 1, particularly for rare variants and for samples of certain genetic ancestr

47 thods and tools for the combined analysis of rare variants and multiple phenotypes.

48 ociation of Alzheimer's disease (AD)-related rare variants APP A673T and ABCA7 rs200538373-C with the

49 The effect sizes of rare variants are 10 times larger than those of common

50 time resolved and genome wide data including rare variants are essential.

51 h non-random errors on association tests for rare variants are unclear, particularly in transmission-

52 We sought to identify additional common and rare variants associated with advanced AMD.

53 hole-genome sequencing to identify groups of rare variants associated with complex traits and disease

54 We identified two novel non-coding rare variants associated with LDL cholesterol (rs1724238

55 ost TE variants were rare, and we find these rare variants associated with local extremes of gene exp

56 As we were not able to detect any rare variants associated with the disease, we sought to

57 A gene-level rare variant association analysis was conducted in SADS

58 t, we introduce an R software package RVFam (Rare Variant association analysis with Family data) desi

59 ome and whole-genome sequencing, methods for rare variant association have been an active area of res

60 more powerful and informative than existing rare variant association methods in the context of domin

61 ped RVTESTS, which implements a broad set of rare variant association statistics and supports the ana

62 e exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346

63 can control for population stratification in rare variant association studies are needed.

64 Rare variant association studies usually need large samp

65 to control for population stratification in rare variant association studies.

66 controlling for population stratification in rare variant association studies.

67 , trans-ancestry meta-analyses of common and rare variant association studies.

68 phenotypes has been hotly debated, but most rare variant association tests (RVATs) do not account fo

69 estigated the impact of genotyping errors on rare variant association tests of family-based sequence

70 Gene-based rare variants association analysis showed enrichment of

71 nd FDR are exceedingly over-conservative for rare variants association studies.

72 lyses will increase the power of common- and rare-variant association studies.

73 ly the most popular statistical test used in rare-variant association studies.

74 -3)), highlighting the challenges of testing rare variant associations and the need for very large sa

75 and efficient study designs for identifying rare-variant associations; and the significance of incid

76 Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting

77 ducted a novel burden test for enrichment of rare variants at the extremes of expression.

78 itional independent signals, including three rare variants, at two previously characterized loci: FGB

79 Sharing rare variants between two individuals is more likely to

80 We did a case-control rare variant burden analysis using 6545 Caucasian contro

81 Using a case-control rare variant burden analysis, 638 (55%) of 1162 sarcoma

82 neurodevelopmental disorders, a significant rare variant burden persists in other genes intolerant o

83 Results from rare variant burden tests showed that familial and popul

84 Phase 3 reference yielded higher accuracy at rare variants, but that the two reference panels were co

85 r mutation screening revealed two truncating rare variants (c.893-1G>A and c.534delT) in CEP78, which

86 acic aortic disease identified another MAT2A rare variant, c.1067G>A (p.Arg356His).

87 A heterozygous rare variant, c.839G>T (p.Ser280Arg), was identified in

88 based studies can be more powerful because a rare variant can be enriched in an extended pedigree and

89 nces in phenotypical characteristics between rare variant carriers and noncarriers were analyzed usin

90 e-causing mutation on a background of benign rare variants challenging.

91 Whole exome sequencing identified two COL6A5 rare variants co-segregating with chronic itch in eight

92 Exome sequencing and rare variant collapsing analysis with 2,936 control exom

93 o gene reached genome-wide significance with rare variant collapsing analysis; however, DEPDC5 (p = 0

94 verexpression outliers have nearby conserved rare variants compared to 8% of non-outliers.

95 that this provides more accurate phasing of rare variants compared with population-based phasing and

96 The complement factor H R1210C rare variant confers the strongest genetic risk for age-

97 Overall, we demonstrate that rare variants contribute to large gene expression change

98 ic variants, especially in families, because rare variants contribute to the age at onset and progres

99 n, and rs61754411 is a previously unreported rare variant contributing to emphysema susceptibility.

100 ng studies of exonic regions aim to identify rare variants contributing to complex traits.

101 To search for rare variants contributing to the risk for EOAD.

102 studies have unique advantages in enriching rare variants, controlling population stratification, an

103 e calling algorithms are less likely to call rare variants correctly, often mistakenly calling hetero

104 sociations indicated that an accumulation of rare variants could explain the signal.

105 ults, we performed a quadratic regression of rare variant count on bins of peripheral blood transcrip

106 The results suggest that the inclusion of rare-variant data/sequencing data in our approach provid

107 Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize

108 arget enrichment to vastly improve NGS-based rare variant detection.

109 However, patients carrying these rare variants differ clinically from noncarriers by an e

110 ication of pathogenic variants in the sea of rare variants discovered as sequencing studies expand in

111 le common variation has been widely studied, rare variant discovery has only recently become feasible

112 more powerful in identifying polymorphisms, rare variants, disease-associations, genetic burden, som

113 Previously reported rare variants do not completely segregate within familie

114 Since rare variants dominate virus populations, we had to care

115 ftware tool allowing rapid identification of rare variant effects on multiple phenotypes, thus paving

116 for de novo mutations, suggesting that most rare-variant effects on schizophrenia risk are inherited

117 is still challenging to accurately genotype rare variants, especially for some rare variants where t

118 VEL (model organism aggregated resources for rare variant exploration).

119 ny studies have attempted to identify causal rare variants, few have reported novel associations.

120 he Wald test and the score test when testing rare variants for association using simulated data.

121 study participants in the DRC, we identified rare variants for complete genome sequencing.

122 Gillespie syndrome (GS) is a rare variant form of aniridia characterized by non-progr

123 sociated protein partners, and then analyzed rare variants from 6112 HCM and 1315 DCM patients and 33

124 ssibility, we identify suggestive common and rare variant genetic associations implying that protecti

125 Recent large-scale common and rare variant genome-wide association studies (GWAS) sugg

126 in multivariate phenotypes to similarity in rare-variant genotypes across a gene.

127 Patients with 2 rare variants had a trend toward younger age at presenta

128 hASER is accurate and improves studies where rare variant haplotypes or allelic expression is needed.

129 distinguish pathogenic variants from benign rare variants have leveraged the genetic code to identif

130 Therefore, ascertaining which rare variants have phenotypic effects remains a major ch

131 high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of

132 roduced into recombinant human NMDARs, these rare variants identified in individuals with neurologic

133 study of certain residues in NMDARs based on rare variants identified in patients is a powerful appro

134 ion testing that jointly assesses common and rare variants, identifying two previously implicated gen

135 A rare variant in APOC3(rs138326449) has been associated w

136 multiple members with TAADs and identified a rare variant in FOXE3 with an altered amino acid in the

137 racteristics of patients with AMD carrying a rare variant in the CFH gene.

138 to the optic disc are more likely to have a rare variant in the CFH gene.

139 Those who inherit a nonsense rare variant in the CPA2 gene had a markedly increased r

140 proach that compares the individual loads of rare variants in 1,042 schizophrenia cases and 961 contr

141 llular loop of NaV1.7, we found an excess of rare variants in a case-control variant-burden study.

142 med to analyze rare variants, where multiple rare variants in a gene region are analyzed jointly.

143 ly significant evidence for an enrichment of rare variants in a protein-based network of 14 genes inv

144 ferences between carriers and noncarriers of rare variants in age at onset of symptoms, the family hi

145 To explore the role of rare variants in AIS susceptibility, exome sequence data

146 Rare variants in CFH, CFI, C9, and C3 contributed to an

147 ected IS patients to have an accumulation of rare variants in ciliary genes.

148 ot previously reported); 7 associations with rare variants in cis, of which 4 are novel; and 6 associ

149 To identify new rare variants in complement genes and determine the func

150 are now being used to understand the role of rare variants in complex traits and to advance the goals

151 Within the WES cohort, the rate of rare variants in CPVT-associated genes was 8.8% compared

152 nd highlights the importance of heterozygous rare variants in determining abnormal blood metabolic ph

153 due to differences in the background rate of rare variants in each gene.

154 e-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, bu

155 assessing the potential burden of additional rare variants in established Mendelian genes and/or GBA,

156 There are existing tools for analyzing rare variants in families but lacking components to hand

157 eno2MP) that links phenotypic information to rare variants in families with Mendelian traits.

158 ing further investigation of both common and rare variants in genes affecting functionally important

159 e found that homozygous but not heterozygous rare variants in genes associated with inherited cardiom

160 s showed an enrichment among IS patients for rare variants in genes with a role in cellular mechanotr

161 Taken together, we propose that rare variants in GIT1, along with other genetic and envi

162 Most rare variants in GluN2A were associated with epilepsy, w

163 e sequencing), we saw an association between rare variants in GRN and DLB.

164 or a hierarchical Bayesian model to identify rare variants in heterogeneous next-generation sequencin

165 Disruptive, damaging ultra-rare variants in highly constrained genes are enriched i

166 Disruptive, damaging ultra-rare variants in highly constrained genes influence the

167 an integrative method for interpretation of rare variants in individual genomes.

168 To assess the role of low-frequency or rare variants in lung cancer development, we analyzed ex

169 ed primary genetic cause had >/=1 additional rare variants in Mendelian PD genes, as compared with no

170 oposed tests to a meta-analysis of noncoding rare variants in Metabochip data on 12,281 individuals f

171 Novel or rare variants in mitochondrial tRNA sequences may be obs

172 Rare variants in more than 30 genes, mostly encoding sar

173 " synonymous ones and strengthen the role of rare variants in neuropsychiatric disease risk.

174 Genetic association analyses of rare variants in next-generation sequencing (NGS) studie

175 Several patients also carried rare variants in other genes previously observed in MAS.

176 ng events and six mono-allelically expressed rare variants in patient-derived fibroblasts and establi

177 t to re-examine the significance of multiple rare variants in patients with hypertrophic cardiomyopat

178 We found an increased burden of rare variants in patients within the untranslated region

179 (n=1411), 9% of gene-positive patients had 2 rare variants in sarcomeric genes but only in 1 case (0.

180 s well as gene sets known to be enriched for rare variants in sequencing studies (PRARE = 0.026).

181 d significant associations between noncoding rare variants in SLC22A3 and low-density lipoprotein and

182 associated with hypertension; additionally, rare variants in SNUPN significantly associated with sys

183 urate imputation and association analysis of rare variants in target samples typed on genotyping arra

184 Consortium data revealed no accumulation of rare variants in the AR cases.

185 Association of rare variants in the CFH, CFI, C9, and C3 genes with AMD

186 We identified two rare variants in the circadian clock gene PERIOD3 (PER3-

187 imed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within

188 Rare variants in the complement factor H (CFH) gene and

189 equencing data of families were filtered for rare variants in the complement factor H (CFH), compleme

190 Rare variants in the complement genes CFH, CFI, C9, and

191 In age-related macular degeneration (AMD), rare variants in the complement system have been describ

192 s and evolutionary theory support a role for rare variants in the etiology of complex traits.

193 GABAA -R genes, we detected an enrichment of rare variants in the GABRG2 gene in RE/ARE patients (5 o

194 ticulitis patients identified two additional rare variants in the gene.

195 intellectual disability are associated with rare variants in the GluN2A and GluN2B (encoded by GRIN2

196 , we investigated the mechanisms by which 25 rare variants in the GluN2A and GluN2B agonist binding d

197 Genetic factors, such as rare variants in the microglial-expressed gene TREM2, st

198 This study therefore searches for rare variants in the TLR8 region and also investigates t

199 d group of 170 unrelated CG patients carried rare variants in this gene.

200 Using rare variants in this way allows us to avoid iterative M

201 Rare variants in TLR8 are not associated with AR.

202 ing this two-step procedure we evaluated all rare variants in two AD cardiomyopathy genes, lamin A/C

203 gle step rephasing of the UK10K panel, using rare variant information, has a downstream impact on pha

204 n clonal iPSCs and fibroblast subclones were rare variants inherited from the parental fibroblasts.

205 ease risk depends on a latent bipartition of rare variants into pathogenic and non-pathogenic variant

206 n proposed for using family data to discover rare variants involved in a disease, a majority of them

207 general and powerful approach to identifying rare variants involved in disease susceptibility.

208 the recent ancestor information captured by rare variants, it is especially powerful in WGS studies.

209 g for segregation and de novo inheritance of rare variants (joint p = 2.3 x 10(-7)).

210 duals in the cohort who carried heterozygous rare variants likely influencing the function of 17 gene

211 Rare variants (<1% minor allele frequency) that segregat

212 One bipolar disorder-associated rare variant (M2145T) in TGEF2 impaired inhibition by th

213 rare variant analysis for low frequency and rare variants (MAF < 0.05).

214 uency variants (0.05>MAF0.005) and aggregate rare variants (MAF<0.005).

215 Our results indicate that rare variants make a disproportionate contribution to ge

216 has sometimes been interpreted to mean that rare variants make negligible contributions to complex t

217 tate cancer and suggest the possibility that rare variants may also have an outsize effect on other c

218 The study of rare variants may enhance our understanding of the genet

219 risk to psychiatric disorders suggests that rare variants might explain a portion of the missing her

220 establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-w

221 h for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potent

222 nce, P</=2.9x10(-7)) and gene-based tests of rare variants (minor allele frequency, <1%; approximatel

223 nts with advanced atrophic AMD carried these rare variants more frequently than patients with neovasc

224 ovides insight into functionally disruptive, rare-variant mutations in human CaMKK2, which have the p

225 dentified significant clusters of non-coding rare variants near NTN1 and NOG and found several rare c

226 Rare variants near the imprinted genes MKRN3 and DLK1 we

227 We restricted our subsequent analysis to rare variants observed at most once in the 1000 Genomes

228 thesis mimicking equine melanoma represent a rare variant of biologically indeterminate or low-grade

229 e a functional link between a case-specific, rare variant of one gene, Crmp4, and several characteris

230 se anterior retinoblastoma is an exquisitely rare variant of retinoblastoma in which the tumor reside

231 erentiated systemic mastocytosis (WDSM) is a rare variant of systemic mastocytosis (SM) characterized

232 ) The genome also contains a large number of rare variants, of which a tiny fraction underlies the in

233 odels the proportion of minor alleles in the rare variants on a linear combination of multiple phenot

234 , so general conclusions about the impact of rare variants on complex traits may be premature.

235 nd-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic

236 required to definitively identify individual rare variants or genes conferring risk for this disorder

237 ntify 52 independently associated common and rare variants (P < 5 x 10(-8)) distributed across 34 loc

238 ollapsing [p = 1.48 x 10(-6)], and burden of rare variants [p = 1.48 x 10(-6)]).

239 ere we report the functional effects of nine rare-variant point mutations that were detected in large

240 Outlier genes were enriched for proximal rare variants, providing a new approach to study large-e

241 In this study, three novel rare variants (R8272Q, S8381C and N8406K) in the C-termi

242 However, multiple rare variants regardless of classification were seen in

243 rlying complex phenotypes, but imputation of rare variants remains problematic.

244 approximately 68% of variation at common and rare variants, respectively, can be captured by imputati

245 t-effectively generated for the detection of rare-variant (RV) associations in families.

246 DNA was used for homozygosity mapping and a rare variant search.

247 se results represent a proof of concept that rare variant sharing patterns can be utilized to phase l

248 e huge human genetic variation resources and rare variant sharing patterns to estimate haplotypes on

249 h MCDR1-linked NCMD shared a haplotype of 14 rare variants spanning 1 Mb of the disease-causing allel

250 xome variant sets which suggests that future rare variant studies may be better focusing their power

251 c inference and modeling of the evolution of rare variants suggest lower effective size on the front,

252 based on a penalized likelihood to discover rare variants that are associated with disease susceptib

253 ses to identify regions of low frequency and rare variants that are associated with DNA methylation l

254 lly significant gene set and gene network of rare variants that are over-represented in MDD, providin

255 on of all protein-coding variants, including rare variants that have not been observed yet in the cur

256 Conversely, rare variants that inactivate the NOS3 or GUCY1A3 genes

257 viduals from Sardinia to identify common and rare variants that influence gene expression and splicin

258 In summary, the present study identified rare variants that might contribute to nsCPO risk and su

259 The present study aimed at identifying rare variants that might contribute to nsCPO risk, via w

260 Additional LOX rare variants that segregated with disease in families w

261 Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the

262 Exome sequencing was performed and rare variants that were predicted to be deleterious and

263 ipelines for quality control and analysis of rare variants; the importance of studying minority popul

264 From genome-wide association studies to rare variants, these findings hold promise for defining

265 equencing study of common, low-frequency and rare variants to associate genetic variations with blood

266 rare, and assessment of the contribution of rare variants to complex traits is hampered by low stati

267 nvestigate both common and under-represented rare variants to develop new approaches to combat the di

268 ons on the contribution of low-frequency and rare variants to human traits.

269 uencing high-risk families to identify novel rare variants to provide greater insights into the molec

270 Drug Register) to assess the contribution of rare variants to treatment response, using clozapine pre

271 44,246 coding-sequence and splice-site ultra-rare variants (URVs) that were unique to individual Swed

272 tical method for cross-phenotype analysis of rare variants using a nonparametric distance-covariance

273 CNVs predicted by CLAMMS at 39 loci (95% of rare variants validate; across 19 common variant loci, t

274 rrors that otherwise make detection of these rare variants very difficult.

275 other approaches that do not explicitly use rare variants we obtain significant gains in phasing acc

276 ncodomain hotspots' unique ability to assess rare variants, we expect our method to become an importa

277 s with strategies for amplifying signal from rare variants, we found that loss-of-function mutations

278 CLCN6 rare variants were also associated with lower systolic B

279 Selected rare variants were assessed for co-segregation in affect

280 Two of the three rare variants were recurrent, located in the GCM2 CCID,

281 associations with increased cancer risk) and rare variants were stratified into classes approximating

282 genotype rare variants, especially for some rare variants where the boundaries of their genotypes ar

283 ciation tests are often performed to analyze rare variants, where multiple rare variants in a gene re

284 C is advantageous for identifying individual rare variants, whereas the Bonferroni and FDR are exceed

285 We identified 17 novel and 74 rare variants, which we classified as pathogenic (11), l

286 tential of larger reference panels to impute rare variants, while recognizing that increasing ethnic

287 For the North Chinese samples, imputation of rare variants with 0.01% < MAF </= 0.5% with the combine

288 For rare variants with 0.01% < MAF </= 0.5%, imputation in t

289 sion data to predict a regulatory effect for rare variants with higher accuracy than models using gen

290 By analysing shared rare variants with hundreds of modern samples from Brita

291 Rare variants with large effect sizes are responsible fo

292 153 previously unreported loci, and several rare variants with large effect sizes.

293 ndividually of small effect size rather than rare variants with large effects on CAD risk.

294 High TraP scores single out extremely rare variants with lower minor allele frequencies than m

295 identified rs146011974G > A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD

296 The tool is based on a method that collapses rare variants within a genomic region and models the pro

297 ve frequency-dependent selection occurs when rare variants within a population are favoured over comm

298 In the present study, we searched for rare variants within or near the DIRAS2 gene that might

299 tics Analysis Workshop 19 (GAW19) Collapsing Rare Variants working group.

300 he 6 contributions from the GAW19 Collapsing Rare Variants working group.