Evidence map›Paper›PMID 26312577›Full record

SynthesisThe Journal of clinical endocrinology and metabolism2015

Bivariate Genome-Wide Association Study Implicates ATP6V1G1 as a Novel Pleiotropic Locus Underlying Osteoporosis and Age at Menarche.

Li-Jun Tan, Zhuo-Er Wang, Ke-Hao Wu, Xiang-Ding Chen, Hu Zhu, Shan Lu, Qing Tian, Xiao-Gang Liu, Christopher J Papasian, Hong-Wen Deng

Open access · bronzeAbstract readMeta-AnalysisMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 3 pooled it
1.1field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Article
  6. Article
  7. Review
  8. Regulatory SNP ofFrontiers in genetics · 2021
    Article
  9. Article
  10. Review
  11. Pleiotropic loci underlying bone mineral density and bone size identified by a bivariate genome-wide association analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020
    Article
  12. Article
  13. Interdisciplinary Work Is Essential for Research on Puberty: Complexity and Dynamism in Action.Journal of research on adolescence : the official journal of the Society for Research on Adolescence · 2019
    Review
  14. Associations ofDisease markers · 2019
    Article
  15. Article
  16. Review
  17. Review
  18. Deficiency ofTheranostics · 2016
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Li-Jun TanLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Zhuo-Er WangLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Ke-Hao WuLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Xiang-Ding ChenLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Hu ZhuLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Shan LuLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Qing TianLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Xiao-Gang LiuLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Christopher J PapasianLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Hong-Wen DengLaboratory of Molecular and Statistical Genetics (L.-J.T., Z.-E.W., K.-H.W., X.-D.C., H.Z., S.L., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; Center of Bioinformatics and Genomics (Q.T., H.-W.D.), School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana 70112; School of Life Science and Technology (X.-G.L.), Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China; and Department of Basic Medical Science (C.J.P.), School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri 64108.
Hunan Normal University · CNTulane University · USXi'an Jiaotong University · CNUniversity of Missouri–Kansas City · US

Funding

Proteome-wide Expression Study of Osteogenic CellsP50AR055081 · NIAMS · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN · 2007 to 2012
$5.0M
ROBUST AND POWERFUL TEST OF CANDIDATE GENES TO BONE MASSR01AR050496 · NIAMS · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN · 2004 to 2013
$3.8M
Epigenomewide DNA Methylation Study for Osteoporosis RiskR01AR059781 · NIAMS · TULANE UNIVERSITY OF LOUISIANA · PI DENG, HONG-WEN · 2012 to 2016
$3.1M
Identification of Proteins Important for Male OsteoporosisR01AR057049 · NIAMS · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN · 2009 to 2013
$2.4M
Genomic search for bone mass QTLsR01AG026564 · NIA · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN · 2007 to 2010
$2.3M
WOMENS HEALTH INITIATIVE-N01WH22110N01WH022110 · WH · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSS, PRENTICE · 1992 to 2006
$1.2M
Genome-wide association study of periodontitisRC2DE020756 · NIDCR · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN, GENCO, ROBERT J · 2009 to 2009
$173k
Genetics of Osteoporotic Fractures in ChineseR03TW008221 · FIC · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN · 2009 to 2011
$171k
FIC NIH HHS R03 TW008221FIC NIH HHS R03TW008221NIAMS NIH HHS P50 AR055081NIAMS NIH HHS P50AR055081NIAMS NIH HHS R01 AR050496NIAMS NIH HHS R01AR050496NIAMS NIH HHS R01 AR057049NIAMS NIH HHS R01AR057049NIAMS NIH HHS R01 AR059781NIA NIH HHS R01 AG026564NIA NIH HHS R01AG026564NIDCR NIH HHS RC2 DE020756NIDCR NIH HHS RC2DE020756WHI NIH HHS N01 WH022110
6 · The paper itself

Abstract

objectiveAge at menarche (AAM) is determined by the overall duration of endocrine-tissue sex hormone exposure levels. Osteoporosis, the most common metabolic bone disease, is characterized primarily by reduced bone mineral density (BMD) and an increased risk of low trauma fractures. Bone was an endocrine organ regulating the synthesis and secretion of sex steroid hormones. The mutual dependence between bone and gonads underscore the importance of genetic approaches to identify novel pleiotropic genetic factors coregulating BMD and AAM. In this study, we performed a bivariate genome-wide association study (GWAS) to explore novel ethnic common loci and/or genes that may influence both AAM and BMD.

methodsWe analyzed genotyping data available for 826 unrelated Chinese subjects using genome-wide human genotyping arrays. After quality control, a total of 702 413 single-nucleotide polymorphisms (SNPs) were tested for association using a bivariate linear regression model. The interesting SNPs were replicated in three independent cohorts including 1728 unrelated Caucasians, 709 African-Americans, and 408 Hispanic-Americans.

resultsWe found four SNPs (rs10817638, rs7851259, rs10982287, and rs4979427), located upstream of the ATP6V1G1 gene, were bivariately associated with hip BMD-AAM (P = 4.90 × 10(-7), P = 1.07 × 10(-6), P = 1.28 × 10(-5), and P = 5.42 × 10(-5), respectively). These four SNPs were replicated in African-Americans, with corresponding values of P = 1.95 × 10(-2), P = 3.18 × 10(-2), P = 2.57 × 10(-2), and P = 3.64 × 10(-2), respectively. rs10817638 and rs10982287 were further replicated in Caucasians (P = 1.76 × 10(-2) and P = 9.42 × 10(-3), respectively) and Hispanic-Americans (P = 8.37 × 10(-3) and P = 1.52 × 10(-3), respectively). Meta-analyses yielded stronger association signals for rs10817638 and rs10982287 with combined values of P = 3.02 × 10(-9) and P = 3.49 × 10(-9), respectively.

conclusionsOur study implicated ATP6V1G1 as a novel pleiotropic gene underlying variation of both BMD and AAM. The findings enhance our knowledge of genetic associations between BMD and AAM and provide a rationale for subsequent functional studies of these implicated genes in the pathophysiology of diseases/traits, such as osteoporosis and AAM.

Indexed as

5' Untranslated RegionsAdolescent DevelopmentGenetic Predisposition to DiseasePolymorphism, Single NucleotideAdolescentAdultAgedAsian PeopleBone DensityChinaFemaleGenetic Association StudiesGenome-Wide Association StudyHumansMenarcheMiddle Aged5' Untranslated RegionsATP6V1G1 protein, humanVacuolar Proton-Translocating ATPases

Identifiers

PMID26312577
PMCPMC4702453
OpenAlexW2128651116

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.