Biology subjects

Tung, J. Y.

Publications and source records attributed to Tung, J. Y..

3 recordsLinked to original sources

bioRxiv2018

Genome-wide association studies on endometriosis and endometriosis-related infertility

Endometriosis affects [~]10% of women of reproductive age. It is characterized by the growth of endometrial-like tissue outside the uterus and is frequently associated with severe pain and infertility. We performed the largest endometriosis genome-wide association study (GWAS) to date, with 37,183 cases and 251,258 controls. All women were of European ancestry. We also performed the first GWAS of endometriosis-related infertility, including 2,969 cases and 3,770 controls. Our endometriosis GWAS study replicated, at genome-wide significance, seven loci identified in previous endometriosis GWASs (CELA3A-CDC42, SYNE1, KDR, FSHB-ARL14EP, GREB1, ID4, and CEP112) and identified seven new candidate loci with genome-wide significance (NGF, ATP1B1-F5, CD109, HEY2, OSR2-VPS13B, WT1, and TEX11-SLC7A3). No loci demonstrated genome-wide significance for endometriosis-related infertility, however, the three most strongly associated loci (MCTP1, EPS8L3-CSF1, and LPIN1) were in or near genes associated with female fertility or embryonic lethality in model organisms. These results reveal new candidate genes with potential involvement in the pathophysiology of endometriosis and endometriosis-related infertility.

genetics↗

bioRxiv2018

Genome-wide association analysis identifies 27 novel loci associated with uterine leiomyomata revealing common genetic origins with endometriosis

Uterine leiomyomata (UL), also known as uterine fibroids, are the most common neoplasms of the reproductive tract and the primary cause for hysterectomy, leading to considerable impact on womens lives as well as high economic burden1,2. Genetic epidemiologic studies indicate that heritable risk factors contribute to UL pathogenesis3. Previous genome-wide association studies (GWAS) identified five loci associated with UL at genome-wide significance (P < 5 x 10-8)4-6. We conducted GWAS meta-analysis in 20,406 cases and 223,918 female controls of white European ancestry, identifying 24 genome-wide significant independent loci; 17 replicated in an unrelated cohort of 15,068 additional cases and 43,587 female controls. Aggregation of discovery and replication studies (35,474 cases and 267,505 female controls) revealed six additional significant loci. Interestingly, four of the 17 loci identified and replicated in these analyses have also been associated with risk for endometriosis - another common gynecologic disorder. These findings increase our understanding of the biological mechanisms underlying UL development, and suggest overlapping genetic origins with endometriosis.

genomics↗

bioRxiv2018

Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways

Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia complaints. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.

genetics↗