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Linear Mixed Models in Genetics · Tutorial 508 of 989

Testing a Variance Component at Zero

Learn to test whether a genetic variance component is zero using the appropriate boundary-aware likelihood-ratio reference distribution.

Intermediate 10 min read

What You'll Learn

  • Explain why a zero variance component is a boundary, not an ordinary interior parameter value
  • State the assumptions behind the one-component boundary-mixture approximation
  • Derive the mixture distribution from a constrained likelihood expansion
  • Calculate mixture-based p-values and critical values for a likelihood-ratio statistic
  • Interpret the test in the context of a genetic mixed model

Why a Zero Variance Requires Special Treatment

In a genetic linear mixed model, a variance component measures the amount of variation assigned to a particular random effect. For example, a genetic effect \(u\) may be modeled as \(u\sim N(0,\sigma_g^2 K)\), where \(K\) is a specified genetic relationship matrix. Testing whether this component is absent means testing \(H_0:\sigma_g^2=0\) against \(H_a:\sigma_g^2>0\).

The difficulty is not that a likelihood-ratio test cannot compare these models. The difficulty is that the null value lies at the edge of the allowable parameter space: a variance cannot be negative. The usual likelihood-ratio reference distribution, a chi-square distribution with one degree of freedom, relies on regularity conditions that include an interior null parameter. At zero, that condition fails. Under appropriate assumptions, the resulting reference distribution is instead a mixture: half its probability is at zero and half follows a chi-square distribution with one degree of freedom.

Definition: A boundary null for a variance component tests whether a nonnegative variance parameter equals zero, such as \(H_0:\sigma_g^2=0\) against \(H_a:\sigma_g^2>0\). The null value is on the boundary of the parameter space \(\{\sigma_g^2:\sigma_g^2\geq 0\}\), rather than in its interior.

The Model and the Likelihood-Ratio Statistic

Consider the Gaussian mixed model

$$ y\sim N(X\beta,\ \sigma_g^2 K+\sigma_e^2 I), $$

where \(y\) is the vector of measured outcomes, \(X\beta\) describes fixed effects, \(K\) is a known genetic relationship matrix, \(\sigma_g^2\geq 0\) is the genetic variance component being tested, and \(\sigma_e^2>0\) is the residual variance. The test compares a null model with \(\sigma_g^2=0\) to an alternative model in which \(\sigma_g^2\) is estimated subject to \(\sigma_g^2\geq 0\).

Let \(\ell_0\) and \(\ell_1\) be the maximized log likelihoods under the null and alternative models, using the same likelihood convention. The likelihood-ratio statistic is

$$ T=2(\ell_1-\ell_0). $$

Because the null model is included in the alternative parameter space, maximizing under the alternative cannot give a lower likelihood, so \(T\geq 0\). The test statistic is often written as \(\mathrm{LR}\) as well. For a restricted maximum likelihood (REML) comparison, the fixed-effects design must be the same in both models; the same boundary issue and mixture reference apply under the corresponding regularity conditions.

Assumptions for the common mixture approximation: The model is correctly specified; the variance component is the single tested component; its covariance pattern is identifiable separately from nuisance parameters; the nuisance parameters are identifiable and regular under the null; and the information for the tested component is positive. The approximation is asymptotic, typically as the sample size grows. For example, if \(K\) is proportional to \(I\), then \(\sigma_g^2 K\) and \(\sigma_e^2 I\) cannot be distinguished as separate sources of variation, and the required identifiability condition fails.

Why the Reference Distribution Is a Mixture

The key feature is the constraint \(\sigma_g^2\geq 0\). A local likelihood approximation makes clear how this constraint changes the usual chi-square result. Write \(\theta\) for the tested variance parameter after accounting for nuisance parameters, so that \(\theta\geq 0\) and the null is \(\theta=0\). Near the null, the log likelihood, after profiling out nuisance parameters, has the approximate form

$$ \ell(\theta)-\ell(0)\ \approx\ \theta U-\frac{1}{2}\theta^2 I_{\mathrm{eff}}, $$

where \(U\) is the efficient score at the null and \(I_{\mathrm{eff}}>0\) is the corresponding information. Under the null, \(U/\sqrt{I_{\mathrm{eff}}}\) is approximately standard normal. Set \(h=\theta\sqrt{I_{\mathrm{eff}}}\) and \(Z=U/\sqrt{I_{\mathrm{eff}}}\). Since \(\theta\geq 0\), the local parameter must satisfy \(h\geq 0\), and the likelihood increment is approximately \(hZ-h^2/2\).

If \(Z\leq 0\), this expression is maximized over \(h\geq 0\) at \(h=0\), giving no likelihood improvement. If \(Z>0\), its maximum occurs at \(h=Z\), giving an increment of \(Z^2/2\). Multiplying the maximized increment by two gives the limiting likelihood-ratio statistic \(\{\max(Z,0)\}^2\). Since a standard normal variable is negative with probability one half and positive with probability one half, this yields the mixture distribution.

$$ T\ \overset{approx}{\sim}\ \frac{1}{2}\chi_0^2+\frac{1}{2}\chi_1^2, $$

Here \(\chi_0^2\) denotes a point mass at zero, not an ordinary continuous chi-square distribution. The other component, \(\chi_1^2\), is a chi-square distribution with one degree of freedom. Thus the limiting statistic is zero with probability one half; with probability one half, it follows the \(\chi_1^2\) distribution. In finite samples this is generally an approximation, not a guarantee of an exact distribution.

Theorem: Under the stated regularity and identifiability conditions, the asymptotic null distribution of the likelihood-ratio statistic for one nonnegative variance component tested at zero is \(\frac{1}{2}\chi_0^2+\frac{1}{2}\chi_1^2\). For an observed \(T>0\), its upper-tail p-value is
$$ p=\frac{1}{2}P(\chi_1^2\geq T)=1-\Phi(\sqrt{T}), $$

where \(\Phi\) is the standard normal cumulative distribution function. The equality follows because a \(\chi_1^2\) variable has the same distribution as the square of a standard normal variable. At \(T=0\), the mixture upper-tail probability is 1, including the mass at zero.

Worked Likelihood-Ratio Tests

Worked Example: Calculating a Mixture-Based P-Value

Suppose a hypothetical study measures a quantitative trait in \(n=240\) individuals. Researchers fit the model above with a prespecified, positive-semidefinite relationship matrix \(K\) that is not proportional to \(I\). They use the same fixed effects in both fits. The maximized log likelihoods are \(\ell_0=-414.42\) for the model with no genetic variance and \(\ell_1=-412.80\) for the model with a genetic variance constrained to be nonnegative. Assume the remaining nuisance parameters are identifiable and the large-sample approximation is suitable.

First calculate the likelihood-ratio statistic:

$$ T=2(\ell_1-\ell_0)=2[-412.80-(-414.42)]=2(1.62)=3.24. $$

For a positive statistic, use the mixture upper tail:

$$ p=1-\Phi(\sqrt{3.24})=1-\Phi(1.800)=0.0359. $$

At significance level \(\alpha=0.05\), this is evidence against \(H_0\) in favor of a positive genetic variance component in this model. It does not establish that the component is biologically causal, nor does it imply that there is a 3.59% probability that \(H_0\) is true.

Worked Example: Seeing Why the Ordinary Chi-Square P-Value Is Wrong

In a second hypothetical analysis, the null-model log likelihood is \(-300.20\), and the alternative-model log likelihood is \(-299.70\). The same fixed effects appear in both models, the covariance component is identifiable, and the model assumptions for the asymptotic test are taken to hold.

The statistic is

$$ T=2[-299.70-(-300.20)]=2(0.50)=1.00. $$

The boundary-mixture p-value is

$$ p=1-\Phi(\sqrt{1.00})=1-\Phi(1.000)=0.1587. $$

If one incorrectly used an ordinary \(\chi_1^2\) reference distribution, the p-value would be \(P(\chi_1^2\geq 1.00)=2[1-\Phi(1.000)]=0.3173\). That is twice the mixture p-value because the mixture assigns only one half of its probability to the continuous \(\chi_1^2\) part. At \(\alpha=0.05\), the correct test does not reject \(H_0\); this is not proof that the genetic variance is exactly zero.

Critical Values and the Testing Decision

The mixture distribution also changes critical values. For a test of size \(\alpha<0.5\), choose a threshold \(c\) whose mixture upper tail is \(\alpha\). For \(c>0\), that tail is one half of the \(\chi_1^2\) upper tail, so \(c\) is the \(1-2\alpha\) quantile of \(\chi_1^2\). For example, at \(\alpha=0.05\), the critical value is approximately 2.706, rather than the ordinary \(\chi_1^2\) critical value of 3.841.

Worked Example: Applying a Five-Percent Critical Value

Consider a third hypothetical cohort with \(n=500\). The relationship matrix is prespecified and identifiable relative to the residual covariance, the same fixed effects are included in both fits, and the other regularity conditions are assumed to be adequate. Suppose the null and alternative log likelihoods are \(-520.00\) and \(-518.60\), respectively.

The statistic is

$$ T=2[-518.60-(-520.00)]=2(1.40)=2.80. $$

The five-percent mixture critical value is the \(0.90\) quantile of \(\chi_1^2\), approximately 2.706. Since \(2.80>2.706\), reject \(H_0\) at the five-percent level. Equivalently, the p-value is \(1-\Phi(\sqrt{2.80})\), approximately \(0.047\). The data provide evidence for a positive genetic variance component under the specified model.

1
Specify the nested models.
Use the same outcome and fixed-effects specification; constrain the tested variance to zero under \(H_0\) and to be nonnegative under \(H_a\).
2
Check the setting.
Confirm that the component is identifiable, nuisance parameters are regular under the null, and the assumptions supporting the asymptotic approximation are plausible.
3
Calculate and calibrate.
Compute \(T=2(\ell_1-\ell_0)\), then use the half-point-mass, half-\(\chi_1^2\) reference distribution for the p-value or critical value.
4
Report the conclusion in context.
Describe evidence for or against a nonzero component under the fitted model, without treating non-rejection as proof of a zero variance.

Interpretation and Common Pitfall

The boundary mixture is not a generic correction for every likelihood-ratio test. It is the standard asymptotic reference in the particular setting of one identifiable, nonnegative variance component tested at zero with otherwise regular nuisance parameters. If the model has several tested variance components, or if a component cannot be identified under the null, this simple mixture need not apply. Those situations require their own analysis rather than an automatic substitution of the half-\(\chi_1^2\) rule.

A common mistake is to say, “The null has one restriction, so use \(\chi_1^2\).” That reasoning treats the tested parameter as if small deviations in both directions from zero were possible. But a variance is constrained to be nonnegative: when the score points toward a negative value, the best allowable fit stays at zero. The resulting probability mass at zero is why the standard interior-parameter reference does not apply. Another mistake is to interpret a nonsignificant result as acceptance of \(H_0\); a failure to reject can reflect limited information as well as a genuinely small component.

Key takeaway: For one identifiable variance component tested at zero, use \(T=2(\ell_1-\ell_0)\) with the asymptotic reference \(\frac{1}{2}\chi_0^2+\frac{1}{2}\chi_1^2\), not an ordinary \(\chi_1^2\) distribution. The mixture follows from restricting the local likelihood maximization to nonnegative values.

Check Your Understanding

Answer each question using the boundary-mixture test and its assumptions.

  1. Why does testing a variance component equal to zero violate the usual interior-parameter condition?
  2. Write the asymptotic null distribution for the likelihood-ratio statistic when one identifiable variance component is tested at zero.
  3. If \(T=2.25\), express the mixture-based p-value using \(\Phi\). What feature of the mixture explains the factor in that expression?
  4. At \(\alpha=0.05\), what \(\chi_1^2\) quantile supplies the critical value for the mixture test?
  5. Why can a genetic variance component fail to be identifiable if its covariance pattern is proportional to the residual covariance pattern?
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