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A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes

Bone Research 2020年第3期8卷 356-364页

作者： Maria A.Christou Georgios Ntritsos Georgios Markozannes Fotis Koskeridis Spyros N.Nikas David Karasik douglas p.kiel Evangelos Evangelou Evangelia E.Ntzani Department of Hygiene and Epidemiology Clinical and Molecular Epidemiology UnitSchool of MedicineUniversity of loanninaloanninaGreece Department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical SchoolHinda and Arthur Marcus Institute for Aging ResearchHebrew SeniorLifeand the Broad Institute of MIT&HarvardCambridgeMAUSA Azrieli Faculty of Medicine Bar llan UniversitySafedIsrael Department of Epidemiology and Biostatistics Imperial College LondonLondonUK Department of Health Services Policy and PracticeCenter for Research Synthesis in HealthSchool of Public HealthBrown UniversityProvidenceRlUSA

Osteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural *** pleiotropy occurs when a single genetic element is associated with more than one *** aimed to identify pleiotropic loci associated with bone mineral density(BMD)and nonbone phenotypes in genome-wide association *** the discovery stage,the NHGRI-EBI Catalog was searched for genome-wide significant associations(p valueproxies of the significantly associated single nucleotide polymorphisms(SNps)(r2=1).We then assessed putative genetic associations of this set of SNps with femoral neck(FN)and lumbar spine(LS)BMD data from the GEFOS *** variants were claimed at a false discovery rateperformed among more than 400000 UK Biobank participants of European ancestry with available genetic and heel bone ultrasound *** the discovery stage,72 BMD-related pleiotropic SNps were identified,and 12 SNps located in 11 loci on 8 chromosomes were replicated in the UK *** SNps were associated,in addition to BMD,with 14 different *** pleiotropic associations were exhibited by rs479844(Ap5B1,O V O L 1 genes),which was associated with dermatological and allergic diseases,and rs4072037(M U C 1 gene),which was associated with magnesium levels and gastroenterological *** conclusion,12 BMD-related genome-wide significant SNps showed pleiotropy with nonbone *** associations can deepen the genetic understanding of bone-related diseases by identifying shared biological mechanisms with other diseases or traits.

关键词： magnesium globally Replication

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