TheHTR1A — 1019C>Ggenotype was associated with major depression in the Utah population. Linkage analysis on Utah pedigrees with strong family histories of major depression including only cases with theHTR1A— 1019G allele revealed a linkage peak on chromosome 10 (maximum HLOD = 4.4). Sequencing of all known genes in the linkage region revealed disease-segregating single-nucleotide polymorphisms (SNPs) inLHPP. LHPPSNPs were also associated with major depression in both Utah and Ashkenazi populations. Consistent with the linkage evidence,LHPPassociations depended onHTR1Agenotype. Lhpp or a product of a collinear brain-specific transcript, therefore, may interact with Htr1a in the pathogenesis of major depression.