Major depression (MD) accounts for substantial worldwide morbidity and mortality. Risk for MD is strongly influenced by genetic risk factors. This project seeks to elucidate the molecular basis of the genetic risk for MD by combining the rich phenotypic measures and sequence data from the CONVERGE (China, Oxford and VCU Experimental Research on Genetic Epidemiology) project. CONVERGE obtained detailed structured interviews on 6,000 Han Chinese women with recurrent MD and 6,000 ethically matched screened controls. Furthermore, in order to interrogate the genome more broadly and more deeply than is possible with genotyping arrays, genotypes will be obtained from low pass (LP) whole genome sequencing. In a sample of the size of CONVERGE, the design provides comprehensive measurement of common variation together with variants at minor allele frequencies below 1-2%, which are poorly imputed from microarray data. LP whole genome sequencing and variant calling will be completed in 2012 using external funding. An ancestry matched sample of 5,000 cases of MD and 5,000 controls is available for replication. We request 4 years of support to conduct i) clinical-phenotypic, ii) molecular-statistical analyses, including gene X environmental interaction analyses with verified environmental risk factors, and iii) replication analyses. In addition to our large sample size, the CONVERGE project has six design features which maximize the probability that we will be able to clarify the nature of the genetic risk factors for MD. We have recruited i) only women who are of ii) Han Chinese ancestry and who have had iii) recurrent illness. For these women, we have carefully assessed iv) four key environmental risk factors and v) a very rich phenotypic profile including important co-morbidities. Finally, our controls are relatively elderly and have been carefully screened to ensure a low liability to depressive illness. The identification of genetic variants which impact o risk for MD would open up the possibility of understanding the pathophysiology of this disorder and developing new methods of treatment and prevention.
Major depression (MD) accounts for substantial worldwide morbidity and mortality and is influence by genetic risk factors. We will elucidate the molecular basis of the genetic risk for MD by studying whole genome DNA sequence in a large sample of Chinese women with and without depression.
|Docherty, A R; Moscati, A; Peterson, R et al. (2016) SNP-based heritability estimates of the personality dimensions and polygenic prediction of both neuroticism and major depression: findings from CONVERGE. Transl Psychiatry 6:e926|
|Edwards, Alexis C; Aggen, Steven H; Cai, Na et al. (2016) CHRONICITY OF DEPRESSION AND MOLECULAR MARKERS IN A LARGE SAMPLE OF HAN CHINESE WOMEN. Depress Anxiety :|
|Lee, Donghyung; Bigdeli, T Bernard; Williamson, Vernell S et al. (2015) DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts. Bioinformatics 31:3099-104|
|CONVERGE consortium (2015) Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature 523:588-91|
|Kendler, K S (2015) A joint history of the nature of genetic variation and the nature of schizophrenia. Mol Psychiatry 20:77-83|
|Kendler, K S; Aggen, S H; Li, Y et al. (2015) The similarity of the structure of DSM-IV criteria for major depression in depressed women from China, the United States and Europe. Psychol Med 45:1945-54|
|Cai, Na; Li, Yihan; Chang, Simon et al. (2015) Genetic Control over mtDNA and Its Relationship to Major Depressive Disorder. Curr Biol 25:3170-7|
|Cai, Na; Chang, Simon; Li, Yihan et al. (2015) Molecular signatures of major depression. Curr Biol 25:1146-56|
|Lee, Donghyung; Williamson, Vernell S; Bigdeli, T Bernard et al. (2015) JEPEG: a summary statistics based tool for gene-level joint testing of functional variants. Bioinformatics 31:1176-82|
|Chen, Jing; Cai, Yiyun; Cong, Enzhao et al. (2014) Childhood sexual abuse and the development of recurrent major depression in Chinese women. PLoS One 9:e87569|
Showing the most recent 10 out of 18 publications