Genetic studies of major depressive disorder: why are there no genome-wide association study findings and what can we do about it?
作者： Douglas F. Levinson , Sara Mostafavi , Yuri Milaneschi , Margarita Rivera , Stephan Ripke
DOI: 10.1016/J.BIOPSYCH.2014.07.029
关键词: Schizophrenia 、 Major depressive disorder 、 Genome-wide association study 、 Single-nucleotide polymorphism 、 Biology 、 Copy-number variation 、 Bipolar disorder 、 Genetics 、 SNP 、 Mood disorders
摘要: Over the past 5 years, genome-wide association study (GWAS) method has produced significant findings that are providing insights into biological pathways involved in disease susceptibility for both schizophrenia and bipolar disorder. Yet, we have no such major depressive disorder (MDD) (1)—the most common of these disorders, causing greatest disability world population. We were asked by editor this journal to comment on why progress been so difficult MDD how can do better. Consider, contrast, remarkable GWAS results achieved (2). First, some background: arrays assay single nucleotide polymorphisms (SNPs) copy number variants (CNVs). (Strong associations observed between rare CNVs but not mood with larger analyses latter now underway. Thus, considered further here.) Common SNPs variations at one nucleic acid position 5% or more chromosomes a population—a frequency achieved, over thousands generations, typically neutral respect survival small effects serious disease. 250,000 1,000,000 tag capture diseases traits, because each genotyped SNP is strongly correlated many nearby SNPs. The statistical power identify depends effect size sample size. Figure 1 illustrates relationship cases studied (plus adequate control subjects) independent several disorders traits. (By independent, mean region set intercorrelated counted only once.) For schizophrenia, multiple datasets
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