Unmeasured confounders (e.g., cortisol, glucagon, insulin) or residual thyroid-independent effects may contribute, though our adjustments for metabolic proxies (which correlate with insulin resistance and hormonal dysregulation) e.g. obesity, lipids, and thyroid autoimmunity, mitigate some concerns. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.