An R port of the RAISS summary-statistic imputation library, described in Julienne H, Shi H, Pasaniuc B, Aschard H (2019), "RAISS: robust and accurate imputation from summary statistics", Bioinformatics 35(22):4837-4839. doi:10.1093/bioinformatics/btz466
Usage
raiss(
refPanel = NULL,
knownZscores,
ldMatrix = NULL,
genotypes = NULL,
lamb = 0.01,
rcond = 0.01,
svdTol = 1e-08,
r2Threshold = 0.6,
minimumLd = 5,
verbose = TRUE
)Arguments
- refPanel
A data frame containing 'chrom', 'pos', 'variant_id', 'A1', and 'A2'. Optional when the LD comes as an
LdMatrixor a genotype panel, whose own variants are used;knownZscoresmust then label chromosomes canonically, as character (e.g."22"). Required with a plainldMatrix, whose rows and columns follow it.- knownZscores
A data frame containing 'chrom', 'pos', 'variant_id', 'A1', 'A2', and 'z' values.
- ldMatrix
A square LD matrix over
refPanel's variants, in its order, or anLdMatrixcovering them. Provide eitherldMatrixorgenotypes, not both.- genotypes
A genotype panel (see
readGenotypes) or aGenotypeMixturecovering the variants, as an alternative toldMatrix. Its dosages are matched torefPanelby variant and allele, mean-imputed and standardized here.- lamb
Regularization term added to the diagonal of the ldMatrix.
- rcond
Eigenvalue cutoff for the pseudo-inverse of the known variants' LD: directions whose ridged eigenvalue is below
rcondtimes the largest are dropped. Applied on both routes, so a genotype panel and the LD matrix computed from it give the same imputation.- svdTol
Relative tolerance below which singular values of the standardized genotypes are treated as numerically zero (genotype route only).
- r2Threshold
R square threshold below which SNPs are filtered from the output.
- minimumLd
Minimum LD score threshold for SNP filtering.
- verbose
Logical indicating whether to print progress information.
Value
A list containing filtered and unfiltered results, and filtered LD matrix (ldMat is NULL on the genotype route).
Details
The imputation model it implements is the one introduced in Pasaniuc B, Zaitlen N, et al. (2014), "Fast and accurate imputation of summary statistics enhances evidence of functional enrichment", Bioinformatics 30(20):2906-2914. doi:10.1093/bioinformatics/btu416
One call imputes one region, from either of the two kinds of LD reference.
The LD can be given as a square correlation matrix or an
LdMatrix, and the imputation then inverts it. Or a genotype
panel from readGenotypes can be given instead, and the
imputation then works from the singular value decomposition of its
standardized dosages, never forming the p x p LD matrix (memory and
compute savings when n << p).
Examples
data(eqtlRegionExample)
X <- eqtlRegionExample$X[, 1:30]
refPanel <- data.frame(chrom = 22, pos = 1:30,
variant_id = paste0("22:", 1:30, ":A:G"), A1 = "A", A2 = "G")
knownZscores <- data.frame(chrom = 22, pos = 1:20,
variant_id = paste0("22:", 1:20, ":A:G"), A1 = "A", A2 = "G",
z = rnorm(20))
raiss(refPanel = refPanel, knownZscores = knownZscores,
ldMatrix = cor(X))
#> Processing LD matrix...
#> IMPUTATION REPORT
#> Variants before filter: 10
#> Non-imputed variants: 0
#> Imputed variants: 10
#> Variants filtered because of low LD score: 8
#> Variants filtered because of low R2: 3
#> Remaining variants after filter: 2
#> $resultNofilter
#> # A tibble: 30 × 9
#> chrom pos variant_id A1 A2 Var raissLdScore raissR2 z
#> <dbl> <int> <chr> <chr> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 22 1 22:1:A:G A G -1 Inf NA 0.837
#> 2 22 2 22:2:A:G A G -1 Inf NA 1.93
#> 3 22 3 22:3:A:G A G -1 Inf NA 0.493
#> 4 22 4 22:4:A:G A G -1 Inf NA 0.0371
#> 5 22 5 22:5:A:G A G -1 Inf NA 0.0279
#> 6 22 6 22:6:A:G A G -1 Inf NA 0.990
#> 7 22 7 22:7:A:G A G -1 Inf NA -0.287
#> 8 22 8 22:8:A:G A G -1 Inf NA -0.218
#> 9 22 9 22:9:A:G A G -1 Inf NA -1.63
#> 10 22 10 22:10:A:G A G -1 Inf NA -2.39
#> # ℹ 20 more rows
#>
#> $resultFilter
#> # A tibble: 22 × 9
#> chrom pos variant_id A1 A2 Var raissLdScore raissR2 z
#> <dbl> <int> <chr> <chr> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 22 1 22:1:A:G A G -1 Inf NA 0.837
#> 2 22 2 22:2:A:G A G -1 Inf NA 1.93
#> 3 22 3 22:3:A:G A G -1 Inf NA 0.493
#> 4 22 4 22:4:A:G A G -1 Inf NA 0.0371
#> 5 22 5 22:5:A:G A G -1 Inf NA 0.0279
#> 6 22 6 22:6:A:G A G -1 Inf NA 0.990
#> 7 22 7 22:7:A:G A G -1 Inf NA -0.287
#> 8 22 8 22:8:A:G A G -1 Inf NA -0.218
#> 9 22 9 22:9:A:G A G -1 Inf NA -1.63
#> 10 22 10 22:10:A:G A G -1 Inf NA -2.39
#> # ℹ 12 more rows
#>
#> $ldMat
#> chr22:32119788:T:C chr22:32119867:T:G chr22:32119961:T:G
#> chr22:32119788:T:C 1.00000000 1.00000000 -0.3896071
#> chr22:32119867:T:G 1.00000000 1.00000000 -0.3896071
#> chr22:32119961:T:G -0.38960714 -0.38960714 1.0000000
#> chr22:32120053:T:C -0.07607973 -0.07607973 -0.1431621
#> chr22:32120593:A:G -0.07607973 -0.07607973 -0.1431621
#> chr22:32120636:T:C -0.16985384 -0.16985384 -0.2327461
#> chr22:32120932:G:A 0.64492502 0.64492502 -0.2595210
#> chr22:32120975:A:G -0.11897144 -0.11897144 -0.1416922
#> chr22:32121290:C:T 0.67670793 0.67670793 -0.5329025
#> chr22:32121498:A:C 0.67670793 0.67670793 -0.5329025
#> chr22:32121635:T:G -0.08086272 -0.08086272 -0.1515361
#> chr22:32121702:A:G -0.18308878 -0.18308878 0.4774493
#> chr22:32121936:G:A -0.17425323 -0.17425323 -0.2013013
#> chr22:32122351:A:G 0.66471365 0.66471365 -0.5068189
#> chr22:32122676:A:G -0.08086272 -0.08086272 -0.1515361
#> chr22:32123055:A:G -0.11897144 -0.11897144 -0.1416922
#> chr22:32123164:T:C 0.41128264 0.41128264 -0.5804376
#> chr22:32123383:T:C 0.53624197 0.53624197 -0.6247040
#> chr22:32123461:T:C -0.09309050 -0.09309050 0.1465514
#> chr22:32123806:C:T 0.53624197 0.53624197 -0.6247040
#> chr22:32124049:G:A 0.53624197 0.53624197 -0.6247040
#> chr22:32124147:A:C 0.53624197 0.53624197 -0.6247040
#> chr22:32120053:T:C chr22:32120593:A:G chr22:32120636:T:C
#> chr22:32119788:T:C -0.07607973 -0.07607973 -0.16985384
#> chr22:32119867:T:G -0.07607973 -0.07607973 -0.16985384
#> chr22:32119961:T:G -0.14316214 -0.14316214 -0.23274610
#> chr22:32120053:T:C 1.00000000 1.00000000 -0.09691283
#> chr22:32120593:A:G 1.00000000 1.00000000 -0.09691283
#> chr22:32120636:T:C -0.09691283 -0.09691283 1.00000000
#> chr22:32120932:G:A -0.01898060 -0.01898060 -0.14868888
#> chr22:32120975:A:G -0.08068061 -0.08068061 0.68622457
#> chr22:32121290:C:T -0.16508211 -0.16508211 -0.24050169
#> chr22:32121498:A:C -0.16508211 -0.16508211 -0.24050169
#> chr22:32121635:T:G 0.98361289 0.98361289 -0.09945025
#> chr22:32121702:A:G -0.07352322 -0.07352322 -0.10944994
#> chr22:32121936:G:A -0.10007160 -0.10007160 -0.09805724
#> chr22:32122351:A:G -0.16810632 -0.16810632 -0.24590866
#> chr22:32122676:A:G 0.98361289 0.98361289 -0.09945025
#> chr22:32123055:A:G -0.08068061 -0.08068061 0.68622457
#> chr22:32123164:T:C -0.20768833 -0.20768833 0.38571586
#> chr22:32123383:T:C -0.21940825 -0.21940825 0.35375073
#> chr22:32123461:T:C -0.03942684 -0.03942684 -0.01498660
#> chr22:32123806:C:T -0.21940825 -0.21940825 0.35375073
#> chr22:32124049:G:A -0.21940825 -0.21940825 0.35375073
#> chr22:32124147:A:C -0.21940825 -0.21940825 0.35375073
#> chr22:32120932:G:A chr22:32120975:A:G chr22:32121290:C:T
#> chr22:32119788:T:C 0.64492502 -0.11897144 0.6767079
#> chr22:32119867:T:G 0.64492502 -0.11897144 0.6767079
#> chr22:32119961:T:G -0.25952101 -0.14169222 -0.5329025
#> chr22:32120053:T:C -0.01898060 -0.08068061 -0.1650821
#> chr22:32120593:A:G -0.01898060 -0.08068061 -0.1650821
#> chr22:32120636:T:C -0.14868888 0.68622457 -0.2405017
#> chr22:32120932:G:A 1.00000000 -0.12097213 0.4578246
#> chr22:32120975:A:G -0.12097213 1.00000000 -0.1631149
#> chr22:32121290:C:T 0.45782464 -0.16311490 1.0000000
#> chr22:32121498:A:C 0.45782464 -0.16311490 1.0000000
#> chr22:32121635:T:G -0.02229749 -0.08220297 -0.1579317
#> chr22:32121702:A:G -0.08442599 -0.07815523 -0.2957522
#> chr22:32121936:G:A -0.09281440 -0.07338441 0.4227297
#> chr22:32122351:A:G 0.44146752 -0.16680800 0.9841509
#> chr22:32122676:A:G -0.02229749 -0.08220297 -0.1579317
#> chr22:32123055:A:G -0.12097213 1.00000000 -0.1631149
#> chr22:32123164:T:C 0.36639669 0.24741886 0.7219857
#> chr22:32123383:T:C 0.33890432 0.23838466 0.8049083
#> chr22:32123461:T:C -0.05761079 -0.03960804 -0.1118759
#> chr22:32123806:C:T 0.33890432 0.23838466 0.8049083
#> chr22:32124049:G:A 0.33890432 0.23838466 0.8049083
#> chr22:32124147:A:C 0.33890432 0.23838466 0.8049083
#> chr22:32121498:A:C chr22:32121635:T:G chr22:32121702:A:G
#> chr22:32119788:T:C 0.6767079 -0.08086272 -0.18308878
#> chr22:32119867:T:G 0.6767079 -0.08086272 -0.18308878
#> chr22:32119961:T:G -0.5329025 -0.15153607 0.47744929
#> chr22:32120053:T:C -0.1650821 0.98361289 -0.07352322
#> chr22:32120593:A:G -0.1650821 0.98361289 -0.07352322
#> chr22:32120636:T:C -0.2405017 -0.09945025 -0.10944994
#> chr22:32120932:G:A 0.4578246 -0.02229749 -0.08442599
#> chr22:32120975:A:G -0.1631149 -0.08220297 -0.07815523
#> chr22:32121290:C:T 1.0000000 -0.15793174 -0.29575216
#> chr22:32121498:A:C 1.0000000 -0.15793174 -0.29575216
#> chr22:32121635:T:G -0.1579317 1.00000000 -0.07735647
#> chr22:32121702:A:G -0.2957522 -0.07735647 1.00000000
#> chr22:32121936:G:A 0.4227297 -0.08038849 -0.16177962
#> chr22:32122351:A:G 0.9841509 -0.16118508 -0.30258029
#> chr22:32122676:A:G -0.1579317 1.00000000 -0.07735647
#> chr22:32123055:A:G -0.1631149 -0.08220297 -0.07815523
#> chr22:32123164:T:C 0.7219857 -0.20174277 -0.33332967
#> chr22:32123383:T:C 0.8049083 -0.21422268 -0.35583510
#> chr22:32123461:T:C -0.1118759 -0.04017078 0.03234585
#> chr22:32123806:C:T 0.8049083 -0.21422268 -0.35583510
#> chr22:32124049:G:A 0.8049083 -0.21422268 -0.35583510
#> chr22:32124147:A:C 0.8049083 -0.21422268 -0.35583510
#> chr22:32121936:G:A chr22:32122351:A:G chr22:32122676:A:G
#> chr22:32119788:T:C -0.17425323 0.66471365 -0.08086272
#> chr22:32119867:T:G -0.17425323 0.66471365 -0.08086272
#> chr22:32119961:T:G -0.20130126 -0.50681889 -0.15153607
#> chr22:32120053:T:C -0.10007160 -0.16810632 0.98361289
#> chr22:32120593:A:G -0.10007160 -0.16810632 0.98361289
#> chr22:32120636:T:C -0.09805724 -0.24590866 -0.09945025
#> chr22:32120932:G:A -0.09281440 0.44146752 -0.02229749
#> chr22:32120975:A:G -0.07338441 -0.16680800 -0.08220297
#> chr22:32121290:C:T 0.42272968 0.98415090 -0.15793174
#> chr22:32121498:A:C 0.42272968 0.98415090 -0.15793174
#> chr22:32121635:T:G -0.08038849 -0.16118508 1.00000000
#> chr22:32121702:A:G -0.16177962 -0.30258029 -0.07735647
#> chr22:32121936:G:A 1.00000000 0.41488387 -0.08038849
#> chr22:32122351:A:G 0.41488387 1.00000000 -0.16118508
#> chr22:32122676:A:G -0.08038849 -0.16118508 1.00000000
#> chr22:32123055:A:G -0.07338441 -0.16680800 -0.08220297
#> chr22:32123164:T:C 0.36747838 0.72764383 -0.20174277
#> chr22:32123383:T:C 0.34368263 0.81708979 -0.21422268
#> chr22:32123461:T:C -0.02241121 -0.08710318 -0.04017078
#> chr22:32123806:C:T 0.34368263 0.81708979 -0.21422268
#> chr22:32124049:G:A 0.34368263 0.81708979 -0.21422268
#> chr22:32124147:A:C 0.34368263 0.81708979 -0.21422268
#> chr22:32123055:A:G chr22:32123164:T:C chr22:32123383:T:C
#> chr22:32119788:T:C -0.11897144 0.41128264 0.53624197
#> chr22:32119867:T:G -0.11897144 0.41128264 0.53624197
#> chr22:32119961:T:G -0.14169222 -0.58043759 -0.62470401
#> chr22:32120053:T:C -0.08068061 -0.20768833 -0.21940825
#> chr22:32120593:A:G -0.08068061 -0.20768833 -0.21940825
#> chr22:32120636:T:C 0.68622457 0.38571586 0.35375073
#> chr22:32120932:G:A -0.12097213 0.36639669 0.33890432
#> chr22:32120975:A:G 1.00000000 0.24741886 0.23838466
#> chr22:32121290:C:T -0.16311490 0.72198572 0.80490828
#> chr22:32121498:A:C -0.16311490 0.72198572 0.80490828
#> chr22:32121635:T:G -0.08220297 -0.20174277 -0.21422268
#> chr22:32121702:A:G -0.07815523 -0.33332967 -0.35583510
#> chr22:32121936:G:A -0.07338441 0.36747838 0.34368263
#> chr22:32122351:A:G -0.16680800 0.72764383 0.81708979
#> chr22:32122676:A:G -0.08220297 -0.20174277 -0.21422268
#> chr22:32123055:A:G 1.00000000 0.24741886 0.23838466
#> chr22:32123164:T:C 0.24741886 1.00000000 0.93235705
#> chr22:32123383:T:C 0.23838466 0.93235705 1.00000000
#> chr22:32123461:T:C -0.03960804 -0.08059521 -0.09259379
#> chr22:32123806:C:T 0.23838466 0.93235705 1.00000000
#> chr22:32124049:G:A 0.23838466 0.93235705 1.00000000
#> chr22:32124147:A:C 0.23838466 0.93235705 1.00000000
#> chr22:32123461:T:C chr22:32123806:C:T chr22:32124049:G:A
#> chr22:32119788:T:C -0.09309050 0.53624197 0.53624197
#> chr22:32119867:T:G -0.09309050 0.53624197 0.53624197
#> chr22:32119961:T:G 0.14655136 -0.62470401 -0.62470401
#> chr22:32120053:T:C -0.03942684 -0.21940825 -0.21940825
#> chr22:32120593:A:G -0.03942684 -0.21940825 -0.21940825
#> chr22:32120636:T:C -0.01498660 0.35375073 0.35375073
#> chr22:32120932:G:A -0.05761079 0.33890432 0.33890432
#> chr22:32120975:A:G -0.03960804 0.23838466 0.23838466
#> chr22:32121290:C:T -0.11187585 0.80490828 0.80490828
#> chr22:32121498:A:C -0.11187585 0.80490828 0.80490828
#> chr22:32121635:T:G -0.04017078 -0.21422268 -0.21422268
#> chr22:32121702:A:G 0.03234585 -0.35583510 -0.35583510
#> chr22:32121936:G:A -0.02241121 0.34368263 0.34368263
#> chr22:32122351:A:G -0.08710318 0.81708979 0.81708979
#> chr22:32122676:A:G -0.04017078 -0.21422268 -0.21422268
#> chr22:32123055:A:G -0.03960804 0.23838466 0.23838466
#> chr22:32123164:T:C -0.08059521 0.93235705 0.93235705
#> chr22:32123383:T:C -0.09259379 1.00000000 1.00000000
#> chr22:32123461:T:C 1.00000000 -0.09259379 -0.09259379
#> chr22:32123806:C:T -0.09259379 1.00000000 1.00000000
#> chr22:32124049:G:A -0.09259379 1.00000000 1.00000000
#> chr22:32124147:A:C -0.09259379 1.00000000 1.00000000
#> chr22:32124147:A:C
#> chr22:32119788:T:C 0.53624197
#> chr22:32119867:T:G 0.53624197
#> chr22:32119961:T:G -0.62470401
#> chr22:32120053:T:C -0.21940825
#> chr22:32120593:A:G -0.21940825
#> chr22:32120636:T:C 0.35375073
#> chr22:32120932:G:A 0.33890432
#> chr22:32120975:A:G 0.23838466
#> chr22:32121290:C:T 0.80490828
#> chr22:32121498:A:C 0.80490828
#> chr22:32121635:T:G -0.21422268
#> chr22:32121702:A:G -0.35583510
#> chr22:32121936:G:A 0.34368263
#> chr22:32122351:A:G 0.81708979
#> chr22:32122676:A:G -0.21422268
#> chr22:32123055:A:G 0.23838466
#> chr22:32123164:T:C 0.93235705
#> chr22:32123383:T:C 1.00000000
#> chr22:32123461:T:C -0.09259379
#> chr22:32123806:C:T 1.00000000
#> chr22:32124049:G:A 1.00000000
#> chr22:32124147:A:C 1.00000000
#>