ライフサイエンスコーパス: rare variant

1 cases and 2.4% of controls had a qualifying rare variant.

2 needed to boost the information content of a rare variant.

3 e commonly used by researchers for analyzing rare variants.

4 enetrance of putatively clinically important rare variants.

5 alues of alpha imply larger effect sizes for rare variants.

6 onally related, genetically independent, and rare variants.

7 e sets that have a significant enrichment of rare variants.

8 onsortia for clarifying risk associations of rare variants.

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

10 erature on the phenotypes accompanying these rare variants.

11 s, possibly weighted, as in burden tests for rare variants.

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

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

14 ypes not only on common variants but also on rare variants.

15 -based emphysema compared with those without rare variants.

16 d by common variants (MAF > 0.01) and 30% by rare variants.

17 not accurate when testing low-frequency and rare variants.

18 We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the B

19 Average effects of rare variants (44% coding) were ~8 times larger than com

20 We identified 127 rare variants across 168 heterozygous genotypes.

21 ene function studies to determine if and how rare variants affect gene function.

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

23 of gene-set analyses showed some support for rare variants affecting synaptic genes.

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

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

26 g were resequenced for the identification of rare variants (allele frequency < 0.05) in 16.9 kB of SE

27 nctionally plausible genes were enriched for rare variants, although no gene achieved study-wide stat

28 that show a marked enrichment of deleterious rare variants among the cases.

29 Here, we perform a series of rare variant analyses across 73,185 women and men to ide

30 These results support the utility of rare variant analyses for identifying disease associatio

31 Using exome sequencing and family based rare variant analyses, we identified a homozygous varian

32 for making decisions about study design for rare variant analyses.

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

34 prediction, genome-wide association studies, rare variants analyses, imputation strategies, meta-anal

35 Our study demonstrates the utility of rare-variant analyses for identifying candidate genes an

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 is work, we present a large-scale exome-wide rare variant analysis of 7,258 individuals (985 cases wi

40 larger, more comprehensive studies enabling rare variant analysis will improve understanding of biol

41 Rare variant and PRS associations, with concomitant func

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

43 Filtering for rare variants and altered expression in proband iPSCs pr

44 nges ahead include a better understanding of rare variants and ancestral differences for integration

45 ociation summary statistics between multiple rare variants and different traits.

46 ion of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function

47 Further evaluation on rare variants and experimentally validated regulatory va

48 ants observed in the cancer genome have been rare variants, and it is common in practice to encounter

49 ucible genome-wide disease associations, and rare-variant approaches have emerged as a viable alterna

50 population level and suggest that studies of rare variants are a fertile ground for discovery of gene

51 methods for testing genetic association with rare variants are being developed.

52 Although rare variants are harder to genotype accurately than com

53 Rare variants are of increasing interest to genetic asso

54 Due to the rarity of the mutant events, rare variants are routinely analyzed on an aggregate lev

55 Europeans, suggesting that height-associated rare variants are under different selection pressure in

56 the so-called collapsing tests for detecting rare variants as highlighted in recent literature.

57 ng research applications based on common and rare variants, as well as genetic syndromes, associated

58 We identified 40 rare variants associated with 21 monogenic genes among 3

59 being widely conducted in order to identify rare variants associated with human diseases and disease

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

61 r suggestive windows that harbored candidate rare variants associated with lung function.Conclusions:

62 To identify rare variants associated with prostate cancer susceptibi

63 e Kernel Association Test (SKAT) to identify rare variant-associated diseases.

64 interaction can boost statistical power for rare variant association mapping in admixed populations.

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

66 ontrols for both burden and dispersion based rare variant association methods.

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

68 robust frequency definition for large-scale rare variant association studies, identify CNVs associat

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

70 Our results provide important insights into rare variant association study designs by providing a la

71 Within this cohort, gene-specific rare variant association tests were performed using 1832

72 nary hypertension (PH), we used the Bayesian rare-variant association method BeviMed.

73 It allows the detected sizes of rare-variant association regions to vary across the geno

74 xibly detects the sizes and the locations of rare-variant association regions without the need to spe

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

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

77 In terms of power for identifying rare variant associations, our LABST uniformly outperfor

78 Here, we introduce multi-trait analysis of rare-variant associations (MTAR), a framework for joint

79 e propose a method to interpret these modest rare-variant associations and to incorporate these assoc

80 les and 791 PheCode phenotypes identified 10 rare-variant associations with p value < 10(-7), includi

81 ms several alternative methods for detecting rare-variant-associations while controlling for the geno

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

83 dies in large samples, now make the study of rare variants at a genome-wide scale feasible.

84 herited risk alleles, including large-effect rare variants at NBN, MRE11 and CTU2 (odds ratio, 28-91)

85 usly reported as FSGS related, we identified rare variants at similar or higher frequencies in contro

86 By testing these and other rare variants at these 13 loci, we experimentally define

87 ducted genome-wide comparisons of common and rare variants between those with schizophrenia and those

88 ta from cases and controls were compared for rare variant burden across 56 cardiomyopathy genes utili

89 diagnosis of rare diseases, the analysis of rare variant burden in complex disorders, and the curati

90 association between copy number variant and rare variant burden measures and TRS did not reach the p

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

92 gene associations in cases versus controls, rare variant burden testing of 56 genes revealed enrichm

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

94 We used rare variant burden tests to evaluate known disease-asso

95 r identifying chromosomal blocks that harbor rare variants but have no ancestry switches.

96 outperforms population-based imputation for rare variants but not for common ones; (3) combining fam

97 he defined haplotype were shown to share the rare variant by targeted Sanger sequencing.

98 rson was homozygous for one of two different rare variants (c.470G>T [p.Cys157Phe] or c.469T>C [p.Cys

99 f assay results, particularly in the case of rare variants captured from patient DNA.

100 for the first time replicating evidence for rare-variant cis-acting protein quantitative trait loci

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

102 hogenic variants and exome-wide and gene-set rare variant collapsing analyses.

103 In our rare variant collapsing analysis, PKD1 was the highest-r

104 This study demonstrates that rare-variant collapsing analyses can validate known gene

105 The multiple rare variant-common disease hypothesis may explain the m

106 Recent studies imply that rare variants contribute to the risk of schizophrenia, h

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

108 pedigree data due to increasing interest in rare variants coupled with the availability of appropria

109 does not provide accurate approximations for rare variant data.

110 ecificity of any genes based on large-effect rare-variant data.

111 e individuals without PI Z, S, or additional rare variants denoted as V(R).

112 addition, we catalogued 52 possibly damaging rare variants detected by NeuroX array in affected indiv

113 This assay for high-sensitivity rare variant detection is appropriate for liquid biopsy

114 We highlight rare-variant discoveries critical to the elucidation of

115 We additionally identify the major areas of rare-variant discovery that will evolve in the coming ye

116 g on the progression of technologies towards rare-variant discovery.

117 Despite larger rare variant effect sizes, rare variants (MAF < 1%) expl

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

119 ing as expression quantitative trait loci to rare variants enriched for gene expression regulatory pa

120 Three novel loci, including two rare variants (European ancestry minor allele frequency

121 Hence, the agglomeration of rare variants, even in the hitherto unannotated and ill-

122 dy, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of

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

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

125 The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in

126 The rare variants found in patients, but not those found exc

127 We analyzed ~250,000 rare variants from 16 independent studies genotyped with

128 We performed analyses of rare variants from 39,146 individuals of European ancest

129 to better understand the diagnostic yield of rare variant genetic testing among a cohort of SCAD surv

130 hibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 anti

131 The rare variants, Glu376Gln and Asn492Ile, which were in co

132 germline PRLR variants, which comprised four rare variants (Gly57Ser, Glu376Gln, Arg453Trp and Asn492

133 ccessfully genotyped SNPs (>96%) and for the rare variants (>99%).

134 signs because of their advantage in studying rare variants has also stimulated more methods developme

135 The contribution of rare variants has not been systematically examined.

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

137 sical single-marker association analyses for rare variants have limited power, and variant-set-based

138 sm spectrum disorders (ASDs); however, these rare variants have not been examined functionally and th

139 (p = 2.6 x 10(-9)), with many harboring CHD rare variants having macrocephaly.

140 We filtered rare variants identified from these cases as well as scr

141 ould not be rescued by RNA encoding damaging rare variants identified in heterotaxy patients.

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

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

144 in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corr

145 fied individuals homozygous-by-descent for a rare variant in RIC1 and, through a guided clinical re-e

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

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

148 mber 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association

149 o sequencing panel to evaluate the burden of rare variants in 56 putative DCM genes in 1040 patients

150 he first large-scale, exome-wide analysis of rare variants in AMD.

151 ed sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with contro

152 We observed no significant enrichment of rare variants in candidate genes (genes encoding compone

153 We hypothesized that rare variants in cardiomyopathy genes contribute to CCM.

154 Unrecognized rare variants in cardiomyopathy-associated genes, partic

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

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

157 the aging process, and that burden of ultra-rare variants in combination with common alleles better

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

159 C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary

160 s in our study validated previous reports of rare variants in complement pathway genes in AMD.

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

162 ies and that carriers of previously reported rare variants in DENND1A, a gene that regulates androgen

163 Analysis of rare variants in family-based studies remains a challeng

164 The association with rare variants in FXYD gene family is novel and highlight

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

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

167 c of gender identity genomics by identifying rare variants in genes associated with sexually dimorphi

168 Eight common and rare variants in genes CFH, C3, ARMS2, COL8A1, and HSPH1

169 Mutations or rare variants in genes expressed in microglial cells, kn

170 IBD at a single center, we found that 3% had rare variants in genes previously associated with pediat

171 s led to the identification of novel or very rare variants in genes, which have not been previously a

172 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of syst

173 Rare variants in GRIN2A encoding the GluN2A subunit are

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

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

176 ing such genes, 122 of 363 cases (33.6%) had rare variants in known disease-associated genes, but 30

177 Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated

178 These analyses together reveal that rare variants in MYH15 represent a likely genetic risk f

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

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

181 how it can be used to prioritize individual rare variants in PCSK9, ANGPTL4 and CETP in the Action t

182 ance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorder

183 w a differential burden of low-frequency and rare variants in restless legs syndrome.

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

185 Among these genetic anomalies, we identified rare variants in SCN5A (1/5:20% in our cases), KIF6 (1/5

186 In genetic studies, we found 40 rare variants in SEMA3A-G and their receptors (PLXNA1-4;

187 Rare variants in TET2 were enriched in the discovery com

188 Identification of rare variants in the CFH and C9 genes in our study valid

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

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

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

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

193 In this study, we have shown enrichment of rare variants in the EDC region in cases compared with c

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

195 ctively discriminating between recurrent and rare variants in the human cancer genome.

196 We also found three rare variants in the KISS1R gene in three patients with

197 Rare variants in the microglia-expressed triggering rece

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

199 We found an association between rare variants in the transcription factor-encoding gene

200 Overall, rare variants in these 12 genes potentially explained 17

201 Rare variants in this set of genes were significantly en

202 a de novo missense variant in BDNF and seven rare variants in TrkB identified in a large cohort of pe

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

204 Understanding the impact of rare variants is essential to understanding human health

205 Understanding the role of rare variants is important in elucidating the genetic ba

206 However, the phenotypic impact of rare variants is under-appreciated as gene function is n

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

208 th the application of statistical methods to rare variants, it is important to understand the strengt

209 In total, 19 rare variant loci spanning 7 genes contributed to an ass

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

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

212 Despite larger rare variant effect sizes, rare variants (MAF < 1%) explain less than 10% of total

213 ng data for 1011 yeast isolates to show that rare variants make a disproportionate contribution to tr

214 We performed a rare variant meta-analysis with published sequencing dat

215 art of the observed phenotypic variance, and rare variants might have also contributed to disease dev

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

217 The novel GPR161 rare variants mislocalized to the primary cilia, dysregu

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

219 Among these, the rare variant NC_000009.11:g.116346115C > A (rs144636307)

220 Rare variants near the imprinted genes MKRN3 and DLK1 we

221 of Shh and Wnt signaling in mice, and novel rare variants of GPR161 can be risk factors for SB in hu

222 We identified six rare variants of GPR161 in six SB cases, of which two of

223 tism-specific" genes, efforts which focus on rare variants of large effect size that are thought to a

224 brain HSE, each heterozygous for one of four rare variants of SNORA31, encoding a small nucleolar RNA

225 Functional characterization of rare variants of uncertain significance in BRIP1 reveale

226 ndividual (singleton) exome harbors over 500 rare variants of unknown significance (VUS) in the splic

227 This can best be achieved by 1) the study of rare variants, often chosen by careful candidate assessm

228 IRADISE ASAS analysis detects the effects of rare variants on alternative splicing.

229 Principal components calculated from rare variants or identity-by-descent segments can correc

230 ccal disease (IMD), but the contributions of rare variants other than those in the complement system

231 lenging due to the large number of noncoding rare variants, our limited understanding of their functi

232 risk genes and pathways show enrichment for rare variants (P = 1.32 x 10(-7)), indicating that addit

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

234 Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and

235 can improve assessment of low-frequency and rare variants, particularly in non-European populations

236 nt towards genetically stratified cohorts of rare variant patients, application of CRISPR technologie

237 ood cancers may result in false estimates of rare variant penetrance from population biobanks.

238 he proportion of cases and controls carrying rare variants per gene.

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

240 d according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity.

241 We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at

242 ycin responses is unknown, we suggest that a rare variant present in the CB4856 strain might cause di

243 Most genes harboring common and/or rare variants previously associated with OCD that were d

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

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

246 To analyze rare variants, region-based multiple-variant aggregate t

247 = 1.32 x 10(-7)), indicating that additional rare variants remain to be identified.

248 toimmune diseases, while the contribution of rare variants remains unclear.

249 blood pressure now comprises >30 genes, with rare variants resulting in monogenic forms of hypertensi

250 motivation for larger-scale investigation of rare-variant risk contributions across major clinical CK

251 One such African ancestry specific rare variant, rs72725854 (A>G/T) (~6% allele frequency)

252 WGS) data for complex traits, we developed a rare variant (RV) non-parametric linkage (NPL) analysis

253 uencing studies have enabled the analysis of rare variants (RVs) associated with complex phenotypes.

254 Non-coding rare variants (RVs) may contribute to Mendelian disorder

255 ne-based analyses were performed for CVs and rare variants (RVs).

256 ided in identifying functional, large-effect rare variants (RVs).

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

258 The Rare Variant Sharing software package RVS implements a s

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

260 hat rely on real-time monitoring to identify rare variants, such as bacterial persistence, drug disco

261 We apply MTAR to rare-variant summary statistics for three lipid traits i

262 After using our rare-variant-tailored methodology to reduce test statist

263 Gene-based rare variant tests implicated a known prostate cancer ge

264 ribution of segregating variants toward more rare variants than are expected without selection (skew)

265 revealed that this contribution is driven by rare variants that arose recently, and that negative sel

266 n the discovery by the Resilience Project of rare variants that confer resistance to Mendelian diseas

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

268 In summary, we report novel genes and rare variants that potentially play a role in prostate c

269 Novel or rare variants that segregated with the affected status w

270 nals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug t

271 but 30 of 363 controls (8.3%) also harbored rare variants that would be classified as "causal" if de

272 ture of each individual comprises common and rare variants that, acting alone and in combination, con

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

274 Negative selection can cause rare variants to have larger per-allele effect sizes tha

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

276 The contributions of rare variants to prostate cancer susceptibility have not

277 disentangle the contributions of common and rare variants to quantitative traits.

278 ws a general tendency of the effect sizes of rare variants towards increasing height, which is contra

279 more than two probands, and burden tests of rare variants using a case-case control design did not y

280 assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dop

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

282 The burden of low-frequency and rare variants was assessed, and in addition, an algorith

283 The prevalence of rare variants was compared between CCM cohorts and The C

284 Frequency of rare variants was compared between late AMD patients and

285 ausal genes and evaluate the contribution of rare variants we used collapsing analysis, in which we c

286 On the basis of the observed distribution of rare variants, we estimate that a two- to three-fold lar

287 itioners of four study participants with the rare variant were alerted to the research findings by le

288 Additionally, rare variants were assessed in genes associated with ver

289 in coding gene PRKN (formerly PARK2) where 7 rare variants were enriched in T1R-affected cases (P (SK

290 ly as the field shifts its attention towards rare variants, which are more likely to be population-sp

291 We integrated large-scale data on rare variants with evolutionary information on ohnolog s

292 yses to identify loci harboring an excess of rare variants with functional connections to a complex t

293 153 previously unreported loci, and several rare variants with large effect sizes.

294 examine the associations between common and rare variants with PWD.

295 We identify gene-level associations of rare variants (with minor allele frequencies of less tha

296 e report ethnic-specific differences in JPH2 rare variants, with GME individuals being at higher risk

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

298 No common or rare variants within the 22q11.2 deletion region were si

299 We further demonstrate that rare variants within the NF1-LRD domain found in a subse

300 Rare variants within these loci hold promise in the iden