Abstract 5091: Genome-Wide Association Study Identifies Loci Associated with a Global Measure of Well-Being
Background: General Well-Being (GWB) is a standardized global measure of psychological and affective domains including depression, anxiety, somaticism, and mood. GWB has been shown to be independently associated with both incident and prevalent coronary heart disease CHD in healthy populations, including high risk African American families. The heritability of GWB is 20%, suggesting a genetic trait locus. We thus performed a genome-wide association study (GWAS) to discover genetic loci for GWB.
Methods: GWB was measured using the18-item GWB Schedule in 1084 healthy African American family members (61% female, mean age 45.8 ± 12 years) identified from probands (N=243) with premature CHD. One million single nucleotide polymorphisms (SNPS) were genotyped using the Illumina Human 1m BeadChip. GWB quantitative phenotype-genotype associations were established using the T-score and Likelihood Ratio Test (LRT) implemented in the ASSOC program in MERLIN (Abecasis, et al).
Results: We identified 8 loci with genome-wide significant associations, including a locus (1q21.2) with genome-wide significant association p values of < e−7 (Table⇓). Potentially important candidate genes in 1q21.2 include MTMR11, a gene highly expressed in CD33+ myeloid (a progenitor cell in the central nervous system), and BOLA1, a gene involved in cell proliferation and cell-cycle regulation. We also found another locus (1p13) containing two SNPS with values of e−6. This region contains the NTNG1 gene, with SNPS that have been associated with schizophrenia and undifferentiated encephalopathy.
Conclusion: The GWAS thus identified two important loci associated with GWB in African American families at increased risk for CHD. These loci contain genes previously shown to be associated with psychiatric disease and central nervous system function.