Confidence interval for linear combination of regression coefficients that are calculated from different variables I would like to estimate a confidence interval for a linear combination of regression coefficients that come from several linear regression models that are calculated from different but correlated variables. For instance, suppose $y_1$ and $x_1$ represent cloud cover and temperature anomalies at one level of the atmosphere as measured by a satellite, and $y_2$ and $x_2$ represent cloud cover and temperature anomalies in a lower level level of the atmosphere. I expect $x_1$ to be correlated with $x_2$. I also expect $y_1$ to be negatively correlated with $y_2$ because the satellite only views the highest clouds. I use OLS regression to determine the relationship
$y_i = \beta_i x_i + \epsilon$ for $i \in {1,2}$
The standard error for the regression slopes is $\sigma_1$ and $\sigma_2$. Now I want to calculate a linear combination of the regression slopes: $C=a_1 \beta_1 +a_2 \beta_2$ where $a_1$ and $a_2$ are real-valued constants. I think that the standard error for $C$ can be calculated from the relationship
$\sigma_C^2 = a_1^2 \sigma_1^2 + a_2^2 \sigma_2^2 + 2a_1 a_2 \sigma_{1,2}$
where $\sigma_{1,2}$ represents the covariance between $\beta_1$ and $\beta_2$. My main question is how does one estimate $\sigma_{1,2}$ given that $\beta_1$ and $\beta_2$ are calculated from different variables?
 A: You may be able to avoid the problem of estimating $\sigma_{12}$ altogether.
Just to be clear, here is my understanding of your setup.  You have a sample of quadruples $(X_1,X_2,Y_1,Y_2).$  Your model of it is that
$$\begin{aligned}
Y_1 &= \beta_1 X_1 + \varepsilon_1 \\
Y_2 &= \beta_2 X_2 + \varepsilon_2
\end{aligned}$$
with $(\varepsilon_1,\varepsilon_2)$ independent of $(X_1,X_2).$  The covariance matrix of the errors exists, but is unknown, and can be written in terms of three parameters as
$$\operatorname{Cov}\pmatrix{\varepsilon_1\\\varepsilon_2} = \pmatrix{\sigma_1^2&\sigma_{12}\\\sigma_{12}&\sigma_2^2}.$$
You have stipulated numbers $a_i$ (they are not estimated from the data) and you wish to estimate
$$\gamma = a_1\beta_1 + a_2\beta_2.$$
One direct way to estimate this quantity is to note that your model implies the relation
$$a_1Y_1 + a_2Y_2 = a_1\beta_1 X_1 + a_2\beta_2 X_2 + (a_1\varepsilon_1 + a_2\varepsilon_2).$$
Under the foregoing assumptions this is a standard regression model for data $(X_1,X_2, a_1Y_1+a_2Y_2)$ which you might fit with, say, ordinary least squares (or any other regression technique appropriate for the assumed distribution of $a_1\varepsilon_1 + a_2\varepsilon_2)$).  That procedure yields estimates $\widehat{a_i\beta_i}$ of the two coefficients, whose sum estimates $\gamma,$ along with an estimated covariance matrix $\widehat\Sigma$ for those estimates, from which you may extract the standard error as
$$\operatorname{se}(\widehat{\gamma}) = \pmatrix{1&1}\widehat\Sigma\pmatrix{1\\1}.$$

It sounds like you might be supposing the $\varepsilon_i$ are negatively correlated: that is, $\sigma_{12}\lt 0.$  If so, and if $a_1a_2 \gt 0,$ the error variance in this model is
$$\operatorname{Var}(a_1\varepsilon_1 + a_2\varepsilon_2) = a_1\sigma_1^2 + a_2\sigma_2^2 + a_1a_2\sigma_{12} \lt a_1\sigma_1^2 + a_2\sigma_2^2,$$
which is a nice thing to have: it means that this linear combination of the $Y_i$ tends to cancel out the errors, giving better estimates of $\gamma$ than if you separately regressed the $Y_i$ against the $X_i.$
