Our study also identified many phenotype-pairs that demonstrated significant genome-wide correlations using the LDSC method, but for which HESS-based genome-wide and local genetic correlations could not be identified. This is unsurprising, given that the sample sizes for these phenotypes were generally below the recommended sample size for HESS analyses (N ≥ 50,000; Shi et al. 2017) Nonetheless, some of these relationships are supported by evidence from clinical and epidemiological studies, and thus may warrant follow-up using larger sample sizes and alternative methods for assessing genetic relationships. For example, we observed a modest positive correlation between self-reported hypothyroidism and major depression (rg = 0.33 ± 0.09, p = 5.0×10−4), as well as trait neuroticism (rg = 0.25 ± 0.06, p = 7.2×10−5). This could be consistent with two different sets of clinical observations. The first is that symptoms of depression are common in individuals with hypothyroidism, and that subclinical hypothyroidism could play a role in a subset of persons diagnosed with major depression; thus cross-contamination of GWAS samples could lead to a biased positive correlation. However, the second observation is that
