I try to do a logistic regression in R and then calculate an odds ratio. I have two groups of people, the first one more strongly exposed to a pollutant than the second one, and the first one developing a certain disease more often.
I just use a set of toy data here. It's easy to generate a model and estimate the significance of influence of the pollutant exposure on developing the disease:
df <- data.frame(disease = as.factor(c(rep(1,100),rep(0,500))),
exposure=c(rnorm(100, mean = 200, sd = 50),
rnorm(500, mean = 100, sd = 20)))
model <- glm(formula = disease ~ exposure, data=df,
family = binomial(link = "logit"))
summary <-summary(model)
OR <- exp(cbind(OddRatio = coef(model), confint(model)))
In R, odds ratios are based on one unit change of the independent variable, e.g. changing the pollutant concentration for 1 mg/ml yields an odds ratio of around 1.1 to 1 in the example.
My question is now, how can I recalculate an odds ratio based on a change for several unit changes? (across the whole range of pollutant exposure)
My first guess was the OR of the new range is OR of one unit change to the power of range size in units.
range <- max(df$exposure)-min(df$exposure)
ORRange <- (OR["exposure",1])^range
In the toy data, the range is about 300. And 1.1 ^ 300 is about 2x10^13, which is quite a lot.
Is this calculation correct, or must it be multiplied (1.1 x 300)?
And what is the mathematical basis to prove the calculation?
That is not how you calculate an odds ratio for different units of change. First, multiply the coefficient on the logit scale (which is what R reports), and then use the exp function on it. Here is an example of calculating the odds ratio for 1, 2, and 3 units of change
unit.change = c(1,2,3)
exp(coef(model)["exposure"]*unit.change)
Related
I want to plot the posterior distribution for data sampled from gamma(2,3) with a prior distribution of gamma(3,3). I am assuming alpha=2 is known. But a graph of my posterior for different values of the rate parameter centers around 4. It should be 3. I even tried with a uniform prior to make things simpler. Can you please spot what's wrong? Thank you.
set.seed(101)
dat <- rgamma(100,shape=2,rate=3)
alpha <- 3
n <- 100
post <- function(beta_1) {
posterior<- (((beta_1^alpha)^n)/gamma(alpha)^n)*
prod(dat^(alpha-1))*exp(-beta_1*sum(dat))
return(posterior)
}
vlogl <- Vectorize(post)
curve(vlogl2,from=2,to=6)
A tricky question and possibly more related to statistics than to programming =). I initially made the same reasoning mistake as you, but subsequently realised to be more careful with the posterior and the roles of alpha and beta_1.
The prior is uniform (or flat) so the posterior distribution is proportional (not equal) to the likelihood.
The quantity you have assigned to the posterior is indeed the likelihood. Plugging in alpha=3, this evaluates to
(prod(dat^2)/(gamma(alpha)^n)) * beta_1^(3*n)*exp(-beta_1*sum(dat)).
This is the crucial step. The last two terms in the product depend on beta_1 only, so these two parts determine the shape of the posterior. The posterior distribution is thus gamma distributed with shape parameter 3*n+1 and rate parameter sum(dat). As the mode of the gamma distribution is the ratio of these two and sum(dat) is about 66 for this seed, we get a mode of 301/66 (about 4.55). This coincides perfectly with the ``posterior plot'' (again you plotted the likelihood which is not properly scaled, i.e. not properly integrating to 1) produced by your code (attached below).
I hope LifeisBetter now =).
But a graph of my posterior for different values of the rate parameter
centers around 4. It should be 3.
The mean of your data is 0.659 (~2/3). Given a gamma distribution with a shape parameter alpha = 3, we are trying to find likely values of the rate parameter, beta, that gave rise to the observed data (subject to our prior information). The mean of a gamma distribution is the shape parameter divided by the rate parameter. 100 observations should be enough to mostly overcome the somewhat informative prior (which had a mean of 1), so we should expect beta to take values somewhere in the region alpha/mean(dat), not 3.
alpha/mean(dat)
#> [1] 4.54915
I'm not going to show the derivation of the posterior distribution for beta without TeX, but it is a gamma distribution that includes the rate parameter from the prior distribution of beta (betaPrior = 3):
set.seed(101)
n <- 100
dat <- rgamma(n, 2, 3)
alpha <- 3
betaPrior <- 3
post <- function(x) dgamma(x, alpha*(n + 1), sum(dat) + betaPrior)
curve(post, 2, 6)
Notice that the mean of beta is at ~4.39 rather than ~4.55 because of the informative prior that had a mean of 1.
I am using t-tests in R to test the significance of the difference in means that arises when adding weights, stratification, and clustering (respectively) to the survey design when utilizing the FGT measure of poverty, which I calculate using the svyfgt function in the convey package. I am running the t-tests by creating vectors for each survey design which include the mean, standard deviation, and sample size, hence, I need to obtain the standard deviation for the svyfgt mean.
In the survey package, there is a svysd function, which is used to calculate the standard deviation when complex survey designs are applied. This value is quite different from the value obtained by simply multiplying the SE by sqrt(n), as shown below:
library(survey)
wel <- c(68008.19, 128504.61, 21347.69,
33272.95, 61828.96, 32764.44,
92545.62, 58431.89, 95596.82,
117734.27)
rmul <- c(16, 16, 16, 16, 16, 16, 16,
20, 20, 20)
splin <- c(23149.64, 23149.64, 23149.64, 23149.64, 23149.64,
21322.23, 21322.23, 21322.23, 21322.23, 21322.23)
survey.data <- data.frame(wel, rmul, splin)
survey_weighted <- svydesign(data = survey.data,
ids = ~wel,
weights = ~rmul,
nest = TRUE)
svymean(~wel, survey_weighted)
svysd(~wel, survey_weighted)
11498*sqrt(10)
In the convey package, there is no equivalent "svyfgtsd" function, and simply multiplying the SE by sqrt(n) would seem to yield the wrong answer (based on the previously shown difference in results between svysd and that expression). Therefore, I am not sure how I might obtain the standard deviation for FGT_0_weighted. Is there a function I am not aware of, or a stats concept that might aid me here?
library(convey)
fgtsurvey_weighted <- convey_prep(survey_weighted)
FGT_0_weighted <- svyfgt(~wel,
fgtsurvey_weighted,
g=0,
abs_thresh = survey.data$splin)
FGT_0_weighted
For reference, I will be using the sd values in t-tests like so (disregard sd values):
FGT_0_unweighted_vector <- c(rnorm(9710, mean = 0.28919, sd = sd_FGT_0))
FGT_0_cluster_vector <- c(rnorm(9710, mean = 0.33259, sd = sd_FGT_0_cluster))
t.test(FGT_0_cluster_vector, FGT_0_unweighted_vector, var.equal = FALSE)
When the poverty threshold is absolute, the FGT is the mean of a binary variable (poor/non-poor); i.e., a proportion. The standard deviation of a binary variable is sqrt( p*(1-p) ).
However, you are probably looking for the standard error (a measure of the sampling error of the FGT estimate), just do SE( FGT_0_weighted ). That's what is used in t-tests.
Taking stratification and clustering into account will alter standard error estimates, while weighting will affect the mean (and all point estimates, like FGT) as well. Using t-tests to test whether mean estimates change makes sense for comparing weighted and unweighted estimates.
Working with sqrt(n) is misleading under complex sampling. The usual n is what is called nominal sample size, but the effective sample size is usually smaller than that (because of cluster sampling.).
A concept related to what you are tying to do is the design effect, but that is not yet implemented for svyfgt (although, for absolute thresholds, you can still get it using svymean).
I have obtained cycle threshold values (CT values) for some genes for diseased and healthy samples. The healthy samples were younger than the diseased. I want to check if the age (exact age values) are impacting the CT values. And if so, I want to obtain an adjusted CT value matrix in which the gene values are not affected by age.
I have checked various sources for confounding variable adjustment, but they all deal with categorical confounding factors (like batch effect). I can't get how to do it for age.
I have done the following:
modcombat = model.matrix(~1, data=data.frame(data_val))
modcancer = model.matrix(~Age, data=data.frame(data_val))
combat_edata = ComBat(dat=t(data_val), batch=Age, mod=modcombat, par.prior=TRUE, prior.plots=FALSE)
pValuesComBat = f.pvalue(combat_edata,mod,mod0)
qValuesComBat = p.adjust(pValuesComBat,method="BH")
data_val is the gene expression/CT values matrix.
Age is the age vector for all the samples.
For some genes the p-value is significant. So how to correctly modify those gene values so as to remove the age effect?
I tried linear regression as well (upon checking some blogs):
lm1 = lm(data_val[1,] ~ Age) #1 indicates first gene. Did this for all genes
cor.test(lm1$residuals, Age)
The blog suggested checking p-val of correlation of residuals and confounding factors. I don't get why to test correlation of residuals with age.
And how to apply a correction to CT values using regression?
Please guide if what I have done is correct.
In case it's incorrect, kindly tell me how to obtain data_val with no age effect.
There are many methods to solve this:-
Basic statistical approach
A very basic method to incorporate the effect of Age parameter in the data and make the final dataset age agnostic is:
Do centring and scaling of your data based on Age. By this I mean group your data by age and then take out the mean of each group and then standardise your data based on these groups using this mean.
For standardising you can use two methods:
1) z-score normalisation : In this you can change each data point to as (x-mean(x))/standard-dev(x)); by using group-mean and group-standard deviation.
2) mean normalization: In this you simply subtract groupmean from every observation.
3) min-max normalisation: This is a modification to z-score normalisation, in this in place of standard deviation you can use min or max of the group, ie (x-mean(x))/min(x)) or (x-mean(x))/max(x)).
On to more complex statistics:
You can get the importance of all the features/columns in your dataset using some algorithms like PCA(principle component analysis) (https://en.wikipedia.org/wiki/Principal_component_analysis), though it is generally used as a dimensionality reduction algorithm, still it can be used to get the variance in the whole data set and also get the importance of features.
Below is a simple example explaining it:
I have plotted the importance using the biplot and graph, using the decathlon dataset from factoextra package:
library("factoextra")
data(decathlon2)
colnames(data)
data<-decathlon2[,1:10] # taking only 10 variables/columns for easyness
res.pca <- prcomp(data, scale = TRUE)
#fviz_eig(res.pca)
fviz_pca_var(res.pca,
col.var = "contrib", # Color by contributions to the PC
gradient.cols = c("#00AFBB", "#E7B800", "#FC4E07"),
repel = TRUE # Avoid text overlapping
)
hep.PC.cor = prcomp(data, scale=TRUE)
biplot(hep.PC.cor)
output
[1] "X100m" "Long.jump" "Shot.put" "High.jump" "X400m" "X110m.hurdle"
[7] "Discus" "Pole.vault" "Javeline" "X1500m"
On these similar lines you can use PCA on your data to get the importance of the age parameter in your data.
I hope this helps, if I find more such methods I will share.
I am using multivariate GAM models to learn more about fog trends in multiple regions. Fog is determined by visibility going below a certain threshold (< 400 meters). Our GAM model is used to determine the response of visibility to a range of meteorological variables.
However, my challenge right now is that I'd really like the y-axis to be the actual visibility observations rather than the centered smoothed. It is interesting to see how visibility is impacted by the covariates relative to the mean visibility in that location, but it's difficult to compare this for multiple locations where the mean visibility is different (and thus the 0 point in which visibility is enhanced or diminished has little comparable meaning).
In order to compare the results of multiple locations, I'm trying to make the y-axis actual visibility observations, and then I'll put a line at the visibility threshold we're interested in looking at (400 m)
to evaluate what the predictor variables values are like below that threshold (eg what temperatures are associated with visibility below 400 m).
I'm still a beginner when it comes to GAMs and R in general, but I've figured out a few helpful pieces so far.
Helpful things so far:
Attempt 1. how to extract gam fit for each variable in model
Extracting data used to make a smooth plot in mgcv
Attempt 2. how to use predict function to reconstruct a univariable model
http://zevross.com/blog/2014/09/15/recreate-the-gam-partial-regression-smooth-plots-from-r-package-mgcv-with-a-little-style/
Attempt 3. how to get some semblance of a y-axis that looks like visibility observations using "fitted" -- though I don't think this is
the correct approach since I'm not taking the intercept into account
http://gsp.humboldt.edu/OLM/R/05_03_GAM.html
simulated data
install.packages("mgcv") #for gam package
require(mgcv)
install.packages("pspline")
require(pspline)
#simulated GAM data for example
dataSet <- gamSim(eg=1,n=400,dist="normal",scale=2)
visibility <- dataSet[[1]]
temperature <- dataSet[[2]]
dewpoint <- dataSet[[3]]
windspeed <- dataSet[[4]]
#Univariable GAM model
gamobj <- gam(visibility ~ s(dewpoint))
plot(gamobj, scale=0, page=1, shade = TRUE, all.terms=TRUE, cex.axis=1.5, cex.lab=1.5, main="Univariable Model: Dew Point")
summary(gamobj)
AIC(gamobj)
abline(h=0)
Univariable Model of Dew Point
https://imgur.com/1uzP34F
ATTEMPT 2 -- predict function with univariable model, but didn't change y-axis
#dummy var that spans length of original covariate
maxDP <-max(dewpoint)
minDP <-min(dewpoint)
DPtrial.seq <-seq(minDP,maxDP,length=3071)
DPtrial.seq <-data.frame(dewpoint=DPtrial.seq)
#predict only the DP term
preds <- predict(gamobj, type="terms", newdata=DPtrial.seq, se.fit=TRUE)
#determine confidence intervals
DPplot <-DPtrial.seq$dewpoint
fit <-preds$fit
fit.up95 <-fit-1.96*preds$se.fit
fit.low95 <-fit+1.96*preds$se.fit
#plot
plot(DPplot, fit, lwd=3,
main="Reconstructed Dew Point Covariate Plot")
#plot confident intervals
polygon(c(DPplot, rev(DPplot)),
c(fit.low95,rev(fit.up95)), col="grey",
border=NA)
lines(DPplot, fit, lwd=2)
rug(dewpoint)
Reconstructed Dew Point Covariate Plot
https://imgur.com/VS8QEcp
ATTEMPT 3 -- changed y-axis using "fitted" but without taking intercept into account
plot(dewpoint,fitted(gamobj), main="Fitted Response of Y (Visibility) Plotted Against Dew Point")
abline(h=mean(visibility))
rug(dewpoint)
Fitted Response of Y Plotted Against Dew Point https://imgur.com/RO0q6Vw
Ultimately, I want a horizontal line where I can investigate the predictor variable relative to 400 meters, rather than just the mean of the response variable. This way, it will be comparable across multiple sites where the mean visibility is different. Most importantly, it needs to be for multiple covariates!
Gavin Simpson has explained the method in a couple of posts but unfortunately, I really don't understand how I would hold the mean of the other covariates constant as I use the predict function:
Changing the Y axis of default plot.gam graphs
Any deeper explanation into the method for doing this would be super helpful!!!
I'm not sure how helpful this will be as your Q is a little more open ended than we'd typically like on SO, but, here goes.
Firstly, I think it would help to think about modelling the response variable, which I assume is currently visibility. This is going to be a continuous variable, bounded at 0 (perhaps the data never reach zero?) which suggests modelling the data as conditionally distributed either
gamma (family = Gamma(link = 'log')) for visibility that never takes a value of zero.
Tweedie (family = tw()) for data that do have zeroes.
An alternative approach would be to model the occurrence of fog; if this is defined as an event <400m visibility then you could turn all your observations into 0/1 values for being a fog event or otherwise. Then you'd model the data as conditionally distributed Bernoulli, using family = binomial().
Having decided on a modelling approach, we need to model the response. This should be done using a multiple regression type of approach, with a GAM including multiple predictors. This way you get to estimate the effect of each potential predictor variable on the response while controlling for the effects of the other predictors. If you just do this using a single predictor at a time, say dewpoint, that variable could well "explain" variation in the data that might be due to another predictor, windspeed say, and you wouldn't know it.
Furthermore, there may well be interactions between predictors that you'll want to control for if they exist, which can only be done in
Then, to finally get to the crux of your problem, having fitted the multi-predictor model to "explain" visibility, you will need to predict from the model for sets of likely conditions. To look at how the visibility varies with dewpoint in a model where other predictor variables have effects, you need to fix the other variables at some reasonable values; one option is to set them to their mean (or modal value in the case of any factor predictor variables), or some other value indicative of typically values for that variable. You'll have to use your domain knowledge for this.
If you have interactions in the model, then you'll need to vary the two variables in the interaction, whilst holding all other variable fixed at some values.
Let's assume you don't have interactions and are interested in dewpoint but the model also includes windspeed. The mean windspeed for the values used to fit the model can be found from the cmX component of the fitted model. Of you could just calculate this from the observed windpseed values or set it to some known number you want to use. Denote the fitted by m, and the data frame with your data in it by df, then we can create new data to predict at over the range of dewpoint, whilst holding windspeed fixed.
mn.windspd <- m$cmX['windspeed']
## or
mn.windspd <- with(df, mean(windspeed))
## or set it some some value
mn.windspd <- 10 # say
Then you can do
preddata <- with(df,
expand.grid(dewpoint = seq(min(dewpoint),
max(dewpoint),
length = 300),
windspeed = mn.windspd))
Then you use this to predict from the fitted model:
pred <- predict(m, newdata = preddata, type = "link", se.fit = TRUE)
pred <- as.data.frame(pred)
Now we want to put these predictions back on to the response scale, and we want a confidence interval so we have to create that first before back transforming:
ilink <- family(m)$linkinv
pred <- transform(pred,
Fitted = ilink(fit),
Upper = ilink(fit + (2 * se.fit)),
Lower = ilink(fit - (2 * se.fit)),
dewpoint = preddata = dewpoint)
Now you can visualised the effect of dewpoint on the response whilst keeping windspeed fixed.
In your case, you will have to extend this to keeping temperature constant also, but that is done in the same way
mn.windspd <- m$cmX['windspeed']
mn.temp <- m$cmX['temperature']
preddata <- with(df,
expand.grid(dewpoint = seq(min(dewpoint),
max(dewpoint),
length = 300),
windspeed = mn.windspd,
temperature = mn.temp))
and then follow the steps above to do the prediction.
For one or two variables varying I have a function data_slice() in my gratia package which will do the above expand.grid() stuff for you so you don't have to specify the mean values of the other covariates:
preddata <- data_slice(m, 'dewpoint', n = 300)
technically this finds the value in the data closest to the median value (for the covariates not varying). If you want means, then do
fixdf <- data.frame(windspeed = mn.windspd, temperature = mn.temp)
preddata <- data_slice(m, 'dewpoint', data = fixdf, n = 300)
If you have an interaction, say between dewpoint and windspeed then you need to vary two variables. This is pretty easy again with expand.grid():
mn.temp <- m$cmX['temperature']
preddata <- with(df,
expand.grid(dewpoint = seq(min(dewpoint),
max(dewpoint),
length = 100),
windspeed = seq(min(windspeed),
max(windspeed),
length = 300),
temperature = mn.temp))
This will create a 100 x 100 grid of values of the covariates to predict at, whilst holding temperature constant.
For data_slice() you'd need to do:
fixdf <- data.frame(temperature = mn.temp)
preddata <- data_slice(m, 'dewpoint', 'windpseed',
data = fixdf, n = 300)
And extending this on to more covariates you want to vary, is also easy following this pattern with expand.grid(); I have yet to implement more than 2 variables varying in data_slice.
I am trying to find a structural break in the mean of a time-series that is skewed, fat-tailed, and heteroskedastic. I apply the Andrews(1993) supF-test via the strucchange package. My understanding is that this is valid even with my nonspherical disturbances. But I would like to confirm this via bootstrapping. I would like to estimate the max t-stat from a difference in mean test at each possible breakpoint (just like the Andrews F-stat) and then bootstrap the critical value. In other words, I want to find my max t-stat in the time-ordered data. Then scramble the data and find the max t-stat in the scrambled data, 10,000 times. Then compare the max t-stat from the time-ordered data to a critical value given by the rank 9,500 max t-stat from the unordered data. Below I generate example data and apply the Andrews supF-test. Is there any way to "correct" the Andrews test for nonspherical disturbances? Is there any way to do the bootstrap I am trying to do?
library(strucchange)
Thames <- ts(matrix(c(rlnorm(120, 0, 1), rlnorm(120, 2, 2), rlnorm(120, 4, 1)), ncol = 1), frequency = 12, start = c(1985, 1))
fs.thames <- Fstats(Thames ~ 1)
sctest(fs.thames)
I'm adding a second answer to analyze the simulated Thames data provided.
Regarding the points from my first general methodological answer: (1) In this case, a log() transformation is clearly appropriate to deal with the extreme skewness of the observations. (2) As the data are heteroscedastic, the inference should be based on HC or HAC covariances. Below I employ the Newey-West HAC estimator, although the data are just heteroscedastic but not autocorrelated. The HAC-corrected inference affects the supF test and the confidence intervals for the breakpoint estimates. The breakpoints themselves and the corresponding segment-specific intercepts are estimated by OLS, i.e., treating the heteroscedasticity as a nuisance term. (3) I did not add any bootstrap or permutation inference as the asymptotic inference appears to be convincing enough in this case.
First, we simulate the data using a particular seed. (Note that other seeds may not lead to such clear-cut breakpoint estimates when analyzing the series in levels.)
library("strucchange")
set.seed(12)
Thames <- ts(c(rlnorm(120, 0, 1), rlnorm(120, 2, 2), rlnorm(120, 4, 1)),
frequency = 12, start = c(1985, 1))
Then we compute the sequence of HAC-corrected Wald/F statistics and estimate the optimal breakpoints (for m = 1, 2, 3, ... breaks) via OLS. To illustrate how much better this works for the series in logs rather than in levels, both versions are shown.
fs_lev <- Fstats(Thames ~ 1, vcov = NeweyWest)
fs_log <- Fstats(log(Thames) ~ 1, vcov = NeweyWest)
bp_lev <- breakpoints(Thames ~ 1)
bp_log <- breakpoints(log(Thames) ~ 1)
The visualization below shows the time series with the fitted intercepts in the first row, the sequence of Wald/F statistics with the 5% critical value of the supF test in the second row, and the residual sum of squares and BIC for the selection of the number of breakpoints in the last row. The code to replicate the graphic is at the end of this answer.
Both supF tests are clearly significant but in levels (sctest(fs_lev)) the test statistic is "only" 82.79 while in logs (sctest(fs_log)) it is 282.46. Also, the two peaks pertaining to the two breakpoints can be seen much better when analyzing the data in logs.
Similarly, the breakpoint estimates are somewhat better and the confidence intervals much narrower for the log-transformed data. In levels, we get:
confint(bp_lev, breaks = 2, vcov = NeweyWest)
##
## Confidence intervals for breakpoints
## of optimal 3-segment partition:
##
## Call:
## confint.breakpointsfull(object = bp_lev, breaks = 2, vcov. = NeweyWest)
##
## Breakpoints at observation number:
## 2.5 % breakpoints 97.5 %
## 1 NA 125 NA
## 2 202 242 263
plus an error message and warnings which all reflect that the asymptotic inference is not a useful approximation here. In contrast, the confidence intervals are quite reasonable for the analysis in logs. Due to the increased variance in the middle segment, its start and end are somewhat more uncertain than for the first and last segment:
confint(bp_log, breaks = 2, vcov = NeweyWest)
##
## Confidence intervals for breakpoints
## of optimal 3-segment partition:
##
## Call:
## confint.breakpointsfull(object = bp_log, breaks = 2, vcov. = NeweyWest)
##
## Breakpoints at observation number:
## 2.5 % breakpoints 97.5 %
## 1 107 119 121
## 2 238 240 250
##
## Corresponding to breakdates:
## 2.5 % breakpoints 97.5 %
## 1 1993(11) 1994(11) 1995(1)
## 2 2004(10) 2004(12) 2005(10)
Finally, the replication code for the figure above is included here. The confidence intervals for the breakpoints in levels are cannot added in the graphic due to the error mentioned above. Hence, only the log-transformed series also has the confidence intervals.
par(mfrow = c(3, 2))
plot(Thames, main = "Thames")
lines(fitted(bp_lev, breaks = 2), col = 4, lwd = 2)
plot(log(Thames), main = "log(Thames)")
lines(fitted(bp_log, breaks = 2), col = 4, lwd = 2)
lines(confint(bp_log, breaks = 2, vcov = NeweyWest))
plot(fs_lev, main = "supF test")
plot(fs_log, main = "supF test")
plot(bp_lev)
plot(bp_log)
(1) Skewness and heavy tails. As usual in linear regression models, the asymptotic justification for the inference does not depend on normality and also holds for any other error distribution given zero expectation, homoscedasticity, and lack of correlation (the usual Gauss-Markov assumptions). However, if you have a well-fitting skewed distribution for your data of interest, then you might be able to increase efficiency by basing your inference on the corresponding model. For example, the glogis package provides some functions for structural change testing and dating based on a generalized logistic distribution that allows for heavy tails and skewness. Windberger & Zeileis (2014, Eastern European Economics, 52, 66–88, doi:10.2753/EEE0012-8775520304) used this to track changes in skewness of inflation dynamics over time. (See ?breakpoints.glogisfit for a worked example.) Furthermore, if the skewness itself is not really of interest then a log or sqrt transformation might also be good enough to make the data more "normal".
(2) Heteroscedasticity and autocorrelation. As usual in linear regression models, the standard errors (or more broadly the covariance matrix) is not consistent in the presence of heteroscedasticity and/or autocorrelation. One can either try to include this explicitly in the model (e.g., an AR model) or treat it as a nuisance term and employ heteroscedasticity and autocorrelation consistent (HAC) covariance matrices (e.g., Newey-West or Andrews' quadratic spectral kernal HAC). The function Fstats() in strucchange allows to plug in such estimators, e.g., from the sandwich package. See ?durab for an example using vcovHC().
(3) Bootstrap and permutation p-values. The "scrambling" of the time series you describe above sounds more like applying permutations (i.e., sampling without replacement) rather than bootstrap (i.e., sampling with replacement). The former is feasible if the errors are uncorrelated or exchangeable. If you are regressing just on a constant, then you can employ the function maxstat_test() from the coin package to carry out the supF test. The test statistic is computed in a somewhat different way, however, this can be shown to be equivalent to the supF test in the constant-only case (see Zeileis & Hothorn, 2013, Statistical Papers, 54, 931–954, doi:10.1007/s00362-013-0503-4). If you want to perform the permutation test in a more general model, then you would have to do the permutations "by hand" and simply store the test statistic from each permutation. Alternatively, the bootstrap can be applied, e.g., via the boot package (where you would still need to write your own small function that computes the test statistic from a given bootstrap sample). There are also some R packages (e.g., tseries) that implement bootstrap schemes for dependent series.