A method for determining the presence or absence of a chromosome trisomy, comprising: (a) obtaining counts of sequence reads mapped to portions of a reference genome, which sequence reads are reads of circulating cell-free nucleic acid from a test sample from a pregnant female; (b) generating a regression for (i) the counts, and (ii) guanine and cytosine (GC) content, for each of the portions of the reference genome for the test sample; (c) assessing the goodness of fit of the counts and the GC content to a non-linear regression or a linear regression, which comprises determining a correlation coefficient from the regression generated in (b), thereby generating an assessment, wherein the assessment is determined according to the correlation coefficient and a correlation coefficient cutoff value, wherein: (i) the correlation coefficient is equal to or greater than the correlation coefficient cutoff value and the assessment is indicative of a linear regression, or (ii) the correlation coefficient is less than the correlation coefficient cutoff value and the assessment is indicative of a non-linear regression; (d) normalizing the counts by a process selected according to the assessment, which comprises: (i) in instances where the assessment is indicative of a linear regression, subtracting the linear regression from the counts, or (ii) in instances where the assessment is indicative of a non-linear regression, subtracting the non-linear regression from the counts, thereby generating normalized counts with reduced GC bias; and (e) determining the presence or absence of a chromosome trisomy according to the normalized counts. (a) obtaining counts of sequence reads mapped to portions of a reference genome, which sequence reads are reads of circulating cell-free nucleic acid from a test sample from a pregnant female; (b) generating a regression for (i) the counts, and (ii) guanine and cytosine (GC) content, for each of the portions of the reference genome for the test sample; (c) assessing the goodness of fit of the counts and the GC content to a non-linear regression or a linear regression, which comprises determining a correlation coefficient from the regression generated in (b), thereby generating an assessment, wherein the assessment is determined according to the correlation coefficient and a correlation coefficient cutoff value, wherein: (i) the correlation coefficient is equal to or greater than the correlation coefficient cutoff value and the assessment is indicative of a linear regression, or (ii) the correlation coefficient is less than the correlation coefficient cutoff value and the assessment is indicative of a non-linear regression; (i) the correlation coefficient is equal to or greater than the correlation coefficient cutoff value and the assessment is indicative of a linear regression, or (ii) the correlation coefficient is less than the correlation coefficient cutoff value and the assessment is indicative of a non-linear regression; (d) normalizing the counts by a process selected according to the assessment, which comprises: (i) in instances where the assessment is indicative of a linear regression, subtracting the linear regression from the counts, or (ii) in instances where the assessment is indicative of a non-linear regression, subtracting the non-linear regression from the counts, thereby generating normalized counts with reduced GC bias; and (i) in instances where the assessment is indicative of a linear regression, subtracting the linear regression from the counts, or (ii) in instances where the assessment is indicative of a non-linear regression, subtracting the non-linear regression from the counts, (e) determining the presence or absence of a chromosome trisomy according to the normalized counts. <EOS>