scholarly journals Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population

SLEEP ◽  
2019 ◽  
Vol 42 (6) ◽  
Author(s):  
Takeshi Nishiyama ◽  
Masahiro Nakatochi ◽  
Atsushi Goto ◽  
Motoki Iwasaki ◽  
Tsuyoshi Hachiya ◽  
...  
Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 409
Author(s):  
Dhruba Tara Maharjan ◽  
Ali Alamdar Shah Syed ◽  
Guan Ning Lin ◽  
Weihai Ying

Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression.


Blood ◽  
2019 ◽  
Vol 133 (9) ◽  
pp. 967-977 ◽  
Author(s):  
Paul S. de Vries ◽  
Maria Sabater-Lleal ◽  
Jennifer E. Huffman ◽  
Jonathan Marten ◽  
Ci Song ◽  
...  

Abstract Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary analysis included all 9 studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using small-interfering RNA and then measuring F7 messenger RNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke (IS), and venous thromboembolism. We identified 2 novel (REEP3 and JAZF1-AS1) and 6 known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, whereas silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of IS. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of IS in the general population.


Diabetes Care ◽  
2020 ◽  
Vol 44 (1) ◽  
pp. 98-106
Author(s):  
Ju-Sheng Zheng ◽  
Jian’an Luan ◽  
Eleni Sofianopoulou ◽  
Fumiaki Imamura ◽  
Isobel D. Stewart ◽  
...  

2012 ◽  
Vol 2 (11) ◽  
pp. e186-e186 ◽  
Author(s):  
T Otowa ◽  
Y Kawamura ◽  
N Nishida ◽  
N Sugaya ◽  
A Koike ◽  
...  

2010 ◽  
Vol 55 (12) ◽  
pp. 816-821 ◽  
Author(s):  
Sosuke Adachi ◽  
Atsushi Tajima ◽  
Jinhua Quan ◽  
Kazufumi Haino ◽  
Kosuke Yoshihara ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daichi Shigemizu ◽  
Risa Mitsumori ◽  
Shintaro Akiyama ◽  
Akinori Miyashita ◽  
Takashi Morizono ◽  
...  

AbstractAlzheimer’s disease (AD) has no cure, but early detection and risk prediction could allow earlier intervention. Genetic risk factors may differ between ethnic populations. To discover novel susceptibility loci of AD in the Japanese population, we conducted a genome-wide association study (GWAS) with 3962 AD cases and 4074 controls. Out of 4,852,957 genetic markers that passed stringent quality control filters, 134 in nine loci, including APOE and SORL1, were convincingly associated with AD. Lead SNPs located in seven novel loci were genotyped in an independent Japanese AD case–control cohort. The novel locus FAM47E reached genome-wide significance in a meta-analysis of association results. This is the first report associating the FAM47E locus with AD in the Japanese population. A trans-ethnic meta-analysis combining the results of the Japanese data sets with summary statistics from stage 1 data of the International Genomics of Alzheimer’s Project identified an additional novel susceptibility locus in OR2B2. Our data highlight the importance of performing GWAS in non-European populations.


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