Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Amsterdam Public Health Research Institute, Amsterdam University Medical Centres, Amsterdam, The Netherlands.
Am J Med Genet B Neuropsychiatr Genet. 2024 Jan;195(1):e32954. doi: 10.1002/ajmg.b.32954. Epub 2023 Jul 12.
Hedonic (happiness) and eudaimonic (meaning in life) well-being are negatively related to depressive symptoms. Genetic variants play a role in this association, reflected in substantial genetic correlations. We investigated the overlap and differences between well-being and depressive symptoms, using results of Genome-Wide Association studies (GWAS) in UK Biobank. Subtracting GWAS summary statistics of depressive symptoms from those of happiness and meaning in life, we obtained GWASs of respectively "pure" happiness (n = 216,497) and "pure" meaning (n = 102,300). For both, we identified one genome-wide significant SNP (rs1078141 and rs79520962, respectively). After subtraction, SNP heritability reduced from 6.3% to 3.3% for pure happiness and from 6.2% to 4.2% for pure meaning. The genetic correlation between the well-being measures reduced from 0.78 to 0.65. Pure happiness and pure meaning became genetically unrelated to traits strongly associated with depressive symptoms, including loneliness, and psychiatric disorders. For other traits, including ADHD, educational attainment, and smoking, the genetic correlations of well-being versus pure well-being changed substantially. GWAS-by-subtraction allowed us to investigate the genetic variance of well-being unrelated to depressive symptoms. Genetic correlations with different traits led to new insights about this unique part of well-being. Our results can be used as a starting point to test causal relationships with other variables, and design future well-being interventions.
快乐（幸福感）和有意义的生活（生活意义感）与抑郁症状呈负相关。遗传变异在这种关联中起作用，反映在大量的遗传相关性中。我们使用英国生物库的全基因组关联研究（GWAS）的结果，研究了幸福感和抑郁症状之间的重叠和差异。从幸福感和生活意义感的 GWAS 汇总统计数据中减去抑郁症状的 GWAS 汇总统计数据，我们获得了“纯”幸福感（n = 216497）和“纯”意义（n = 102300）的 GWAS。对于这两种情况，我们都确定了一个全基因组显著的 SNP（rs1078141 和 rs79520962）。减去后，纯幸福感的 SNP 遗传力从 6.3%降至 3.3%，纯意义的 SNP 遗传力从 6.2%降至 4.2%。幸福感衡量标准的遗传相关性从 0.78 降至 0.65。纯幸福感和纯意义感与与抑郁症状强烈相关的特征（包括孤独感和精神障碍）在遗传上不再相关。对于其他特征，包括 ADHD、教育程度和吸烟，幸福感与纯幸福感的遗传相关性发生了很大变化。GWAS 减去允许我们研究与抑郁症状无关的幸福感的遗传变异。与不同特征的遗传相关性为幸福感的这一独特部分提供了新的见解。我们的研究结果可作为测试与其他变量因果关系和设计未来幸福感干预措施的起点。
