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 ng from deleterious coding and conserved non-coding variants.

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

4 redicting the functional consequences of non-coding variants.

5 ing potential functional consequences of non-coding variants.

6 ese algorithms when predicting the impact of coding variants.

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

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

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

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

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

12 d provides a functional basis to analyze new coding variants.

13 x trait association studies focused on rare, coding variants.

14 eloped tool to aid in the discovery of novel coding variants.

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

16 identifying and interpreting regulatory non-coding variants.

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

18 pathogenicity or regulatory functions of non-coding variants.

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

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

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

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

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

24 helial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular si

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

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

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

28 coding 5', 3' UTRs and intronic regions plus coding variants acting together can change 5HT transport

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

30 hyperactivity disorder-associated human DAT coding variant Ala559Val (hDAT A559V) results in anomalo

31 re a rare human DA transporter (DAT; SLC6A3) coding variant, Ala559Val.

32 in African-American SLE patients using these coding variants, along with tagging polymorphisms in TNF

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

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

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

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

37 PP1 SNPs (tagging SNPs (n=12) from HapMap, 4 coding variants and 6 SNPs in the promoter region) were

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

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

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

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

42 nges to transcript sequences and isoforms by coding variants, and changes to transcript abundance by

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

44 detailed functional characterization of the coding variants, AnnTools searches for overlaps with reg

45 To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequ

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

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

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

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

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

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

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

53 D was observed, with the strongest signal at coding variant Arg381Gln (allele frequency, 2.5% in CD v

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

55 for direct genotyping of 85 972 polymorphic coding variants as well as 48 known GWAS SNPs.

56 To identify rare coding variants associated with a large increase in risk

57 ,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 x 1

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

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

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

61 Second, several non-coding variants associated with cognitive functions map

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

63 We identified low-frequency coding variants associated with fasting proinsulin conce

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

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

66 HumanExome Beadchip, in search of functional coding variants associated with lipids traits.

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

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

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

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

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

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

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

74 Novel associations were detected with coding variants at rs35937854 in AA (PAA = 1.49 x 10(-9)

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

76 tion spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg], c.4487G>A [p.C

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

93 ified the previously reported non-synonymous coding variants (E921D and E993V) which also resulted in

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

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

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

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

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

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

100 Overexpression of an Epac2 rare coding variant, found in human subjects diagnosed with a

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

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

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

104 Analysis of coding variants from two affected individuals identified

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

106 Burden analysis for coding and non-coding variants gave nominal associations with diagnosis

107 a SERT haplotype defined by 2 nonsynonymous coding variants [Gly-39 and Lys-152 (GK)].

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

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

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

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

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

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

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

115 of SERT with L90V-A(3)AR, a hyperfunctional coding variant identified in subjects with autism spectr

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

117 Rare coding variants identified exclusively in patients were

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

119 en examined the effect of the non-synonymous coding variants identified on their cell surface APA act

120 A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs12

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

122 Sequence analysis identified a coding variant in exon 2 that segregates with harlequin

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

124 filtering, we identified a single-nucleotide coding variant in the feline leukemia virus subgroup C c

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

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

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

128 We report that a coding variant in the LHR-D (long homologous repeat D) r

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

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

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

132 1.08, P = 3.9 x 10(-7)), and novel damaging coding variants in 3 genes previously tagged by GWAS eff

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

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

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

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

137 ter enzyme function, we expressed 80 protein-coding variants in an isogenic mammalian system and meas

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

139 Screening of a control population for novel coding variants in CACNA1C, CDKL5, HOXA1, SHANK3, TSC1,

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

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

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

143 Of the many nonsynonymous coding variants in CFH, two are most strongly associated

144 we identified multiple gain-of-function SERT coding variants in children with ASD.

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

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

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

148 h ICH and identify three rare, nonsynonymous coding variants in four patients that are not present in

149 ls in the general population who harbor rare coding variants in genes for Mendelian disorders and who

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

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

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

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

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

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

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

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

158 ately 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and M

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

160 69 x 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9

161 Identifying coding variants in LOAD will facilitate the creation of

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

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

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

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

166 Prioritized coding variants in SORL1 were detected by targeted reseq

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

168 First, we assessed the contribution of rare coding variants in the 25 genes to the risk of RA in a p

169 s suggest that African Americans with common coding variants in the APOL1 gene are 5-29 times more li

170 Coding variants in the APOL1 gene are associated with ki

171 It is a longstanding puzzle why non-coding variants in the complement factor H (CFH) gene ar

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

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

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

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

176 Here, we report a comprehensive analysis of coding variants in the NCI-60 panel of cell lines identi

177 Combinations of coding variants in these genes were not associated with

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

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

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

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

182 dendrite complexity, and exemplify how rare coding variants, in addition to their disease relevance,

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

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

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

186 However, the mechanisms by which these non-coding variants increase risk for T2D are not well-estab

187 Finally, in our data, this coding variant is also associated with AD susceptibility

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

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

190 order, and depression, and suggest that rare coding variants may contribute significantly to risk of

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

192 These findings confirm in vivo that DISC1 coding variants modulate centrosomal PCM1 localization,

193 ing combinations of two of the nonsynonymous coding variants most strongly associated with AMD risk,

194 Coding variants (n = 211) were genotyped to test whether

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

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

197 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain c

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

199 A common coding variant of grainyhead like transcription factor 3

200 Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase

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

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

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

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

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

206 Three common non-coding variants of the gene (rs2903692, rs725613 and rs1

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

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

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

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

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

212 mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variat

213 The effects of rare coding variants on COL4A1 biosynthesis were compared to

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

215 No coding variants or variants within or near splice sites

216 th genotype imputation, was used to identify coding variants other than the apolipoprotein E (APOE) e

217 al research has focused primarily on protein-coding variants, owing to the difficulty of interpreting

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

219 ween TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03).

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

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

222 mutation frequencies, with 2,000-4,000 novel coding variants per exome.

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

224 DHD cohort, we identified a hDAT (human DAT) coding variant, R615C, located in the distal C terminus

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

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

227 The first is expected: coding variants reported in disease-related databases si

228 An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) conf

229 the strongest association for EA is the same coding variant rs1143679 (log(10)Bayes factor=20, P = 6.

230 findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM-SLE a

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

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

233 1; OR, 1.71; p = 8.2 x 10(-10) ), an imputed coding variant (rs2233290) at position 151 (Pro-->Ala) i

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

235 A DNA coding variant (rs3736265) and a 3'UTR-resident regulato

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

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

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

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

240 ghly significant association of a synonymous coding variant rs7853758 (L461L) within the SLC28A3 gene

241 ound two correlated and predicted non-benign coding variants (rs8100241 in exon 2 and rs8108174 in ex

242 Another PPARGC1A coding variant (rs8192678) showed statistical interactio

243 Further, we demonstrate that the coding variant's effect is largely dependent on an inter

244 k to human brain, and includes another DISC1 coding variant, Ser704Cys.

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

246 Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% con

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

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

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

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

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

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

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

254 Taken together, our analyses identify a CR1 coding variant that influences episodic memory decline;

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

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

257 he numerous nonsynonymous, single nucleotide coding variants that are present in each human individua

258 d macular degeneration (AMD) than functional coding variants that directly influence the alternative

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

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

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

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

263 10(-8) in meta-analysis), highlighting novel coding variants that may underlie inborn errors of metab

264 Third, we identified low-frequency coding variants that might account for allelic heterogen

265 Frequent coding variants that modestly impair PC1/3 function mild

266 to comprehensively identify and type protein-coding variants throughout the genome.

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

268 ate contribution of low-frequency and common coding variants to the risk of RA by dense genotyping of

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

270 Rs17863783 is a synonymous coding variant Val209Val within the functional UGT1A6.1

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

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

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

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

275 All synonymous coding variants were benign polymorphisms with no appare

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

277 Over 70% of all expressed coding variants were identified from RNA-seq, and compar

278 Multiple rare coding variants were identified including one nonsense a

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

280 for extending these studies to include rare coding variants, which often have more marked functional

281 In contrast, coding variants, which span 1% of the genome, explained

282 that the number of discovered nonsynonymous coding variants will reach 100,000 in each population af

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

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

285 We observed a strong enrichment of coding variants with a nominal signal of association wit

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

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

288 This suggests that low-frequency coding variants with large effect sizes (OR >2) may not

289 To identify low-frequency coding variants with large effects on LOAD risk, we carr

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

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

292 eased effective sample size by 8.3-11.4% for coding variants with minor allele frequency <1%.

293 Larger sample sizes may identify coding variants with more moderate effects.

294 Rare coding variants with putative functional impact are obse

295 D, suggesting that examples of low-frequency coding variants with robust effects on both lipids and C

296 essed the association of these and other VWF coding variants with von Willebrand factor (VWF) and fac

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 me sequencing, to identify novel segregating coding variants within the linked region.