ライフサイエンスコーパス: coding variant

1 nts were grouped by gene, as were functional coding variants.

2 , such as BRCA1, and many common, mostly non-coding variants.

3 been achieved by studying rare de novo (DN) coding variants.

4 lleles, but no analogous code exists for non-coding variants.

5 ls in assessing the pathogenic impact of non-coding variants.

6 ial to elucidate the functional roles of non-coding variants.

7 identifying and interpreting regulatory non-coding variants.

8 , filtering and annotation of coding and non-coding variants.

9 pathogenicity or regulatory functions of non-coding variants.

10 retained 439 obesity-enriched low-frequency coding variants.

11 n effect that is independent of any observed coding variants.

12 ferent tools on functional annotation of non-coding variants.

13 ly for single-nucleotide and other small non-coding variants.

14 eles remains difficult, particularly for non-coding variants.

15 ent at much higher number in the genome than coding variants.

16 ng from deleterious coding and conserved non-coding variants.

17 searches and categorize both coding and non-coding variants.

18 redicting the functional consequences of non-coding variants.

19 ing potential functional consequences of non-coding variants.

20 ese algorithms when predicting the impact of coding variants.

21 iants, as well as rare, population-specific, coding variants.

22 (eQTLs), microRNA (miRNA)-binding sites and coding variants.

23 hallenge for such assessments as compared to coding variants.

24 d identified five regulatory clusters of non-coding variants.

25 e of interrogating low-frequency and protein-coding variants.

26 rved in brains of AD patients carrying TREM2 coding variants.

27 g associations with 21 rare or low-frequency coding variants.

28 ions that consist of a massive number of non-coding variants.

29 ch human genome carries tens of thousands of coding variants.

30 rden tests of nonsynonymous/loss-of-function coding variants.

31 When looking solely at coding variants, a total of 28 nonsynonymous variants we

32 ndings suggest that recurrent, low-frequency coding variants account for a minority of the unexplaine

33 low-cost evaluation of CNVs, coding, and non-coding variants across candidate regions of interest.

34 The discovery of low-frequency coding variants affecting the risk of coronary artery di

35 io et al. reveal new mechanisms by which non-coding variants alter the activity of the anti-diabetic

36 the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, a

37 NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding do

38 By demonstrating that this common non-coding variant alters FOXE1 expression, we have identifi

39 Using published common variant, rare coding variant and copy number variant data, we examined

40 Rare, high-penetrance coding variants and common, low-penetrance non-coding va

41 Establishing causal links between non-coding variants and human phenotypes is an increasing ch

42 key to dissecting the allelic effects of non-coding variants and their contribution to phenotypic div

43 In this review, we discuss the human non-coding variants and their contributions to human disease

44 ropean ancestry women: low-frequency protein-coding variants and X-chromosome variants.

45 e arose from common noncoding variants, rare coding variants, and copy-number variants affecting gene

46 a valuable resource for studies of GWAS, non-coding variants, and enhancer-mediated regulation.

47 thm designed to annotate both coding and non-coding variants, and has been shown to outperform other

48 uency) and rare (<1% minor allele frequency) coding variants are associated with MI.

49 ethods for predicting disease-associated non-coding variants are faced with a chicken and egg problem

50 Rare TCF4 coding variants are found in individuals with Pitt-Hopki

51 e that common, low frequency and rare CHRNA5 coding variants are independently associated with nicoti

52 Regulatory and coding variants are known to be enriched with associatio

53 n the Hutterites suggest that these rare non-coding variants are likely to mediate their effects on l

54 e show that genes with cis-configurations of coding variants are more frequent than genes with trans-

55 ods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery o

56 For one, non-coding variants are present at much higher number in the

57 The vast majority of coding variants are rare, and assessment of the contribu

58 enced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects

59 study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS.

60 athogenicity prediction tools tackle all non-coding variants as one amorphic class and/or are not cal

61 ,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 x 1

62 We identified rare coding variants associated with Alzheimer's disease in a

63 requency (minor allele frequency (MAF) < 5%) coding variants associated with BMI.

64 g SCN5A, we identified novel common and rare coding variants associated with cardiac conduction.

65 sess whether the candidate loci contain rare coding variants associated with CRP levels and (2) perfo

66 X3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke.

67 trate that most of the low-frequency or rare coding variants associated with lipids are population sp

68 ineteen white heterozygotes for five non-S/Z coding variants associated with lower alpha-1 antitrypsi

69 es, we identified two previously undescribed coding variants associated with lower platelet count: a

70 trated its effectiveness in prioritizing non-coding variants associated with medical phenotypes.

71 wo different contexts: the prediction of non-coding variants associated with Mendelian and with compl

72 egulatory functions for 423 of 565 (75%) non-coding variants associated with platelet traits and we d

73 entified 16 common variants (8 of which were coding variants) associated with one or more WBC traits,

74 Our approach identifies novel coding variant associations and extends the allelic spec

75 ding 3 novel loci and 14 East Asian-specific coding variant associations.

76 moted the production of a presumably protein-coding variant at the expense of an mRNA with nonsense-m

77 n the heart yields an additional 13 rare QRS coding variants at 12 loci.

78 Here, we assessed whether coding variants at these 28 genes affect QT interval in

79 of defense-associated receptors, identifying coding variants between SCA6 and NA32 which could contri

80 ly on "gold standard" genes harboring causal coding variants, but such gold standards may be biased a

81 sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (

82 raises key questions regarding how a single coding variant can contribute to this diversity of clini

83 he biologic mechanism by which a common, non-coding variant can distally regulate a gene and contribu

84 tation of the functional consequences of non-coding variants can be greatly enhanced by catalogs of r

85 Protein-coding variants can be highlighted to support interpreta

86 c and germline variants, and discuss how non-coding variants can be interpreted on a large-scale thro

87 ther functional classification of HNF1A rare coding variants can inform models of diabetes risk predi

88 Our results support the hypothesis that rare coding variants can pinpoint causal genes within known g

89 -level functional consequence scores for non-coding variants can refine the mechanism of known functi

90 Ps is likely to be a marker for another, non-coding, variant causally related to breast cancer risk.

91 duals were homozygous for the ultra-rare non-coding variant chr8:96046914 T > C; rs575462405, whereas

92 e population sequencing data in studying non-coding variant classes.

93 heritance of large genomic deletions and non-coding variants: compound inheritance at a locus consist

94 The odds ratio for qualifying non-coding variants considered independently from coding var

95 dy was to evaluate whether additional PNPLA3 coding variants contribute to NAFLD susceptibility, firs

96 Our findings suggest that rare coding variants contribute to the genetic architecture o

97 s, we sought to test the hypothesis that non-coding variants contribute to this phenotype.

98 is) and determination of support for protein-coding variants contributing to risk in previously publi

99 pical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mu

100 The number of potentially pathogenic coding variants did not influence disease duration or si

101 e distribution of the probability that a non-coding variant disrupts regulatory activities.

102 ion (429 trios) study to reveal a second non-coding variant distal to RET and a non-coding allele on

103 We identified 395 220 coding variants down to 0.05% frequency [57% non-synonym

104 de strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large ef

105 ity of the Evolutionary Action score of TP53-coding variants (EAp53) to predict the impact of TP53 mu

106 Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we s

107 ls with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional a

108 Annotating genetic variants, especially non-coding variants, for the purpose of identifying pathogen

109 , much of the focus has been on rare protein-coding variants, for which potential impact can be estim

110 Rare coding variants found in at least 2 data sets were genot

111 ial impact of the considerable number of non-coding variants found in Whole Genome Sequencing runs.

112 tified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P

113 Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3

114 Here we report a compilation of coding variants from 1,055 healthy Korean individuals (K

115 Analysis of coding variants from two affected individuals identified

116 y (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[

117 nctional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD a

118 Rare non-coding variants have been associated with extreme gene e

119 Rare coding variants have been proven to be one of the signif

120 mulants inhibit DA reuptake and multiple DAT coding variants have been reported in patients with neur

121 ergic neurotransmission, and a number of DAT coding variants have been reported in several DA-related

122 Non-coding variants have been shown to be related to disease

123 ings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture,

124 variants to leprosy susceptibility, protein-coding variants have not been systematically investigate

125 nts (RE) and genes perturbed by acquired non-coding variants, here we establish epigenomic and transc

126 s implicated by the increased burden of rare coding variants highlight the involvement of neurodevelo

127 carried potentially pathogenic novel or rare coding variants identified by sequencing or an expanded

128 Rare coding variants identified exclusively in patients were

129 We integrate chromatin contacts with non-coding variants identified in schizophrenia genome-wide

130 T), to predict the regulatory targets of non-coding variants identified in studies of eQTLs.

131 unctionally validated a novel pathogenic non-coding variant in a small family with a previously unres

132 onse (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trai

133 ross the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA ex

134 increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15;

135 The strongest coding variant in schizophrenia GWAS is a missense mutat

136 les of European ancestry, is the only common coding variant in the canonical transcript, in non-Afric

137 Among these were a coding variant in the gene encoding prostaglandin E2 syn

138 We hypothesized that a synonymous coding variant in the IL-1 receptor antagonist gene (IL1

139 Here we identify a rare coding variant in the KALRN gene region that encodes the

140 In one family we find a coding variant in the MSX1 gene which is predicted damag

141 ding variants and common, low-penetrance non-coding variants in 13 genes are known to underlie HSCR r

142 We identified 14 coding variants in 13 genes, of which 8 variants were in

143 Rare coding variants in 24 genes that play roles in enteric n

144 1.08, P = 3.9 x 10(-7)), and novel damaging coding variants in 3 genes previously tagged by GWAS eff

145 Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians.

146 the effects of functionally independent non-coding variants in a coordinated gene regulatory network

147 e found 3 independent associations with rare coding variants in ADAMTS13: rs148312697 (beta, -32.2%;

148 We followed-up 34 coding variants in an additional 2350 MI cases and 2318

149 tion meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclini

150 e regulatory role of enhancer-associated non-coding variants in cancer epigenome, and to facilitate t

151 stigation of functional contributions of non-coding variants in cancer epigenome.

152 We review the current understanding of non-coding variants in cancer, including the great diversity

153 ous studies have noted the importance of non-coding variants in cancer.

154 Replication of protein-coding variants in candidate genes was observed for 2 pr

155 nt aggregate contribution of rare and common coding variants in CHRNA9 to the risk for ND (SKAT-C: P=

156 These findings implicate the effect of rare coding variants in CLCN6 in BP variation and offer new i

157 ese regions, we investigate the role of rare coding variants in clinically relevant quantitative card

158 Both common variants and low-frequency coding variants in CPN1 were associated with a fibrinoge

159 Coding variants in epigenetic regulators are emerging as

160 , coding alteration only, or coding plus non-coding variants in experimentally predicted regulatory r

161 of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interacti

162 etic sequencing efforts have identified rare coding variants in genes in the triglyceride-rich lipopr

163 methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooki

164 ntified two rare, recessive and hypermorphic coding variants in GPATCH3, a gene of unidentified funct

165 age genome-wide association study of protein-coding variants in Han Chinese, of whom were 7,048 lepro

166 encing is identifying growing numbers of non-coding variants in human disease studies, but the lack o

167 Given the current interest in coding and non-coding variants in human disease, MDiGS fulfills a niche

168 ification and characterization of causal non-coding variants in human genomes is challenging and requ

169 e an excess of homozygosity and rare protein-coding variants in Iceland.

170 found no significant contribution from rare coding variants in independent schizophrenia cohorts gen

171 69 x 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9

172 Identifying coding variants in LOAD will facilitate the creation of

173 Here we describe that rare coding variants in lupus-risk genes are present in most

174 Several nonsynonymous coding variants in MINT2 have been identified in autism

175 in strain-specific transcription levels and coding variants in neonatal and adult cortical tissue.

176 to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including

177 , our study outlines the contribution of non-coding variants in neutrophil GM-CSF signaling and the p

178 mediated by a combination of common and rare coding variants in RIN3 and suggest that RIN3 may contri

179 Our findings suggest that protein-coding variants in selected GWAS loci did not contribute

180 ed significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and g

181 Four novel coding variants in SLC22A12, p.Asn136Lys, p.Thr225Lys, p

182 Prioritized coding variants in SORL1 were detected by targeted reseq

183 Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1,

184 Twenty loci contained rare coding variants in the 95% credible intervals.

185 Two coding variants in the apo L1 gene (APOL1) are strongly

186 Coding variants in the APOL1 gene are associated with ki

187 Two coding variants in the apolipoprotein L1 (APOL1) gene (t

188 In addition, we detected rare coding variants in the C9, SPEF2 and BCAR1 genes, which

189 lated genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor e

190 Furthermore, we found evidence that coding variants in the known susceptibility gene ABCA7,

191 sequencing excluded other likely pathogenic coding variants in the linked interval.

192 Coding variants in the lysyl oxidase-like 1 (LOXL1) gene

193 Coding variants in the triggering receptor expressed on

194 population-matched control individuals, and coding variants in this gene are exceptionally rare in t

195 Coding variants in TMEM175 are likely to be responsible

196 e (AD), exemplified by the identification of coding variants in triggering receptor expressed on myel

197 ear TTN, our observation of rare deleterious coding variants in TTN associated with QT interval show

198 By performing a meta-analysis of rare coding variants in whole-exome sequences from 4,133 schi

199 of variants (most of which are low-frequency coding variants) in a cohort of patients with neurodegen

200 equencing failed to identify any shared rare coding variants, in this region or elsewhere.

201 tributes to the prediction of functional non-coding variants, including expression quantitative trait

202 te the frequency distribution of all protein-coding variants, including rare variants that have not b

203 chnologies for functional annotations of non-coding variants, including the methods for genome-wide m

204 Individuals with coding variants involving either TBX4 or FGF10 also harb

205 The occurrence of rare coding variants involving TBX4 or FGF10 with the putativ

206 tional effects of disease-associated protein-coding variants is increasingly routine.

207 that the join effects of the regulatory and coding variants largely contribute to the divergence of

208 nts near NTN1 and NOG and found several rare coding variants likely to affect protein function, inclu

209 has, thus far, failed to identify other rare coding variants linked to CAD.

210 noncoding variants and/or by rare but severe coding variants, many de novo.

211 Rare deleterious coding variants may increase risk for COPD, but multiple

212 Rare and low-frequency functional protein-coding variants (minor allele frequency, <=5%) measured

213 r the evaluation of the functionality of non-coding variants, most of them used 'black boxes' methods

214 We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect s

215 ificant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [

216 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain c

217 Low-frequency coding variants, not detected by GWAS, are predicted to

218 A common coding variant of grainyhead like transcription factor 3

219 We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs38

220 Inheritance of a coding variant of the protein tyrosine phosphatase nonre

221 pha-1 antitrypsin deficiency shows that rare coding variants of large effect also influence COPD susc

222 Exome sequencing identified three novel coding variants of potential significance in the RIC3, R

223 , and examined the linkage structure to find coding variants of SLC22A1 that mediate independent asso

224 Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SER

225 with human pigmentation characteristics two coding variants of TPC2, rs35264875 (encoding M484L) and

226 ticipants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency

227 nt sibling pairs identified 17 nonsynonymous coding variants, of which 1 located in SMAP1 and 3 in RI

228 e examined the contribution of low-frequency coding variants on a genome-wide level.

229 ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically

230 Predicting the regulatory effects of non-coding variants on candidate genes is a key step in eval

231 o test the effects of rare and low-frequency coding variants on hematological traits, we analyzed hem

232 ently, a novel partial loss-of-function AKT2 coding variant (p.Pro50Thr) was identified that is nearl

233 tients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln)

234 ngapore and Japan, we identified four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile an

235 Discovered protein-coding variants, particularly low-frequency and rare one

236 ompound inheritance at a locus consisting of coding variants plus non-coding ones is described.

237 reduced zinc transport activity. ZIP12 rare coding variants predicted to be deleterious were associa

238 Non-coding variants present a unique challenge for such asse

239 mpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that th

240 We show that 71% of all rare non-coding variants previously proposed as causal lead to re

241 ndocytic phenotype exhibited by the ADHD DAT coding variant, R615C.

242 n lung health and disease, and to assay rare coding variants relevant to the UK population.

243 Non-coding variants remain particularly difficult to interpr

244 ns, prioritize the functional effects of non-coding variants remains a challenge.

245 whole-genome sequencing to reveal shared non-coding variants, revealed one potentially functional var

246 The coding variant rs1229984( *)T has previously been associ

247 notyping, we have identified a low-frequency coding variant rs2076349 (V527M) in the laminin subunit

248 Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated w

249 We identified 4 non-coding variants (rs3808851, rs10974787, rs10974788 and r

250 d fine-mapping analyses identified a protein-coding variant, rs4788863 in SLC16A5, that was associate

251 -wide-significant signal of selection at the coding variant rs601338 in FUT2 (p = 9.16 x 10(-9)).

252 value = 1.9 x 10(-8)), which clusters with a coding variant rs6030 (P-value = 7.8 x 10(-7)).

253 Similar experiments indicate that the CDHR3 coding variant rs6967330 increases CDHR3 protein surface

254 tionally, we identified a rare distinct G6PD coding variant (rs76723693, p.Leu353Pro, MAF = 0.5%; -0.

255 el rare (minor allele frequency = 0.16%) CRP-coding variant (rs77832441-A; p.Thr59Met) was associated

256 Most of these newly identified coding variants show suggestive association (P<0.05) wit

257 In humans, we identified a nonsynonymous coding variant, single nucleotide polymorphism rs6175392

258 Among these non-coding variants, somatic insertions are among the least

259 In the first-stage discovery, rare coding variants (splicing, stop-gain, stop-loss, nonsyno

260 The interpretation of non-coding variants still constitutes a major challenge in t

261 leprosy, highlighting the merits of protein-coding variant studies for complex diseases.

262 reover, the ability to rescue the DAT(R615C) coding variant suggests that manipulating DAT traffickin

263 ylitis, and provide direct evidence of a non-coding variant that alters expression of the prostagland

264 nclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD

265 eQTLs in the DGRP, including one common non-coding variant that lowers enteric infection susceptibil

266 fied a previously not reported low-frequency coding variant that was associated with morbid obesity i

267 tperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a v

268 uence we identified two new X-linked protein coding variants that arose de novo in BALB/cByJ, in the

269 Finally, we identified four novel non-coding variants that cause disease through the disruptio

270 Non-coding variants that disrupt splicing are extremely chal

271 otential therapeutic approach to correct DAT coding variants that exhibit trafficking dysregulation.

272 genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2.

273 as been highlighted by the identification of coding variants that increase risk for Alzheimer's disea

274 Conditional analyses did not find protein-coding variants that may be responsible for GWAS signals

275 10(-8) in meta-analysis), highlighting novel coding variants that may underlie inborn errors of metab

276 Two coding variants, TMEM175 p.M393T (odds ratio [OR] = 1.37

277 ' and 3' UTRs contributed more strongly than coding variants to risk for BD, both in pedigrees and in

278 Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing n

279 Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplica

280 In addition, a TREM2 R47H coding variant was recently identified as a risk factor

281 oding variants considered independently from coding variants was 3.7 (95% CI 1.7-9.4).

282 Technical progress in interpretation of non-coding variants: we briefly describe some of the technol

283 The remaining 22 rare coding variants were associated with increased risk of n

284 CKD-EPI eGFR and genotypes of three APOL1 coding variants were available.

285 All synonymous coding variants were benign polymorphisms with no appare

286 Common and rare SCN5A coding variants were examined for association with PR an

287 No BALB/cJ-specific X-linked protein coding variants were found, implicating instead a varian

288 Rare coding variants were identified in the CFH, PUS7, RXFP2,

289 -coding regions and potentially point to non-coding variants, whereas their functional interpretation

290 We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs1

291 and gene-based analyses were carried out for coding variants with a minor allele frequency less than

292 In addition, we examined eight coding variants with counts >/=5 and saw evidence for as

293 Low-frequency coding variants with intermediate effect size may accoun

294 We associated damaging coding variants with low GM-CSF induced STAT5 stimulatio

295 Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in

296 Common coding variants with minor allele frequencies (MAF) >1%

297 Lymphocyte tyrosine phosphatase, a coding variant within the tyrosine phosphatases, is know

298 ng glucose levels, including a nonsynonymous coding variant within Tpcn2.

299 We can now routinely identify coding variants within individual human genomes.

300 ast genetic diversity as naturally occurring coding variants, yet the impact of these variants on pro