<p>The familial relevance of depression is a critical aspect, with evidence suggesting a substantial hereditary component. Investigating the inheritance patterns within families can provide valuable insights into the genetic underpinnings of depression. To gain a new perspective on the genetics underpinning of depression, we conducted a novel analysis of the Genetics of Recurrent Early-onset Depression (GenRED) dataset including 683 U.S. Caucasian families, each with one proband with recurrent early-onset major depression and at least one sibling with depression. Using the MERLIN tool, we identified 37 genomic markers with nominal significance linkage to early-onset recurrent depression. The findings differ from prior analyses of GenRED using a different analytical tool. Our findings highlight the variability and potential discrepancies that can arise from using different analytical tools on the same dataset. Given the chance of microsatellites undergoing duplication, mutations, and amplification errors, our two-point analysis can be more robust compared to the previous multipoint analysis. Also, one limitation is genetic admixture; studies with more homogenous ethnic groups are warranted.</p>