SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:gup.ub.gu.se/161395"
 

Search: onr:"swepub:oai:gup.ub.gu.se/161395" > Meta-Analysis of Ge...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Medina-Gomez, Carolina (author)

Meta-Analysis of Genome-Wide Scans for Total Body BMD in Children and Adults Reveals Allelic Heterogeneity and Age-Specific Effects at the WNT16 Locus.

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-07-05
  • Public Library of Science (PLoS),2012

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/161395
  • https://gup.ub.gu.se/publication/161395URI
  • https://doi.org/10.1371/journal.pgen.1002718DOI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P=4.1×10(-11) observed for rs917727 with minor allele frequency of 0.37. We sought replication for all SNPs located ±500 kb from rs917727 in 11,052 additional individuals from five independent studies including children and adults, together with de novo genotyping of rs3801387 (in perfect linkage disequilibrium (LD) with rs917727) in 1,014 mothers of children from the discovery cohort. The top signal mapping in the surroundings of WNT16 was replicated across studies with a meta-analysis P=2.6×10(-31) and an effect size explaining between 0.6%-1.8% of TB-BMD variance. Conditional analyses on this signal revealed a secondary signal for total body BMD (P=1.42×10(-10)) for rs4609139 and mapping to C7orf58. We also examined the genomic region for association with skull BMD to test if the associations were independent of skeletal loading. We identified two signals influencing skull BMD variation, including rs917727 (P=1.9×10(-16)) and rs7801723 (P=8.9×10(-28)), also mapping to C7orf58 (r(2)=0.50 with rs4609139). Wnt16 knockout (KO) mice with reduced total body BMD and gene expression profiles in human bone biopsies support a role of C7orf58 and WNT16 on the BMD phenotypes observed at the human population level. In summary, we detected two independent signals influencing total body and skull BMD variation in children and adults, thus demonstrating the presence of allelic heterogeneity at the WNT16 locus. One of the skull BMD signals mapping to C7orf58 is mostly driven by children, suggesting temporal determination on peak bone mass acquisition. Our life-course approach postulates that these genetic effects influencing peak bone mass accrual may impact the risk of osteoporosis later in life.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Kemp, John P (author)
  • Estrada, Karol (author)
  • Eriksson, JoelGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xerjoe (author)
  • Liu, Jeff (author)
  • Reppe, Sjur (author)
  • Evans, David M (author)
  • Heppe, Denise H M (author)
  • Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xvanli (author)
  • Herrera, Lizbeth (author)
  • Ring, Susan M (author)
  • Kruithof, Claudia J (author)
  • Timpson, Nicholas J (author)
  • Zillikens, M Carola (author)
  • Olstad, Ole K (author)
  • Zheng, Hou-Feng (author)
  • Richards, J Brent (author)
  • St Pourcain, Beate (author)
  • Hofman, Albert (author)
  • Jaddoe, Vincent W V (author)
  • Smith, George Davey (author)
  • Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlomat (author)
  • Gautvik, Kaare M (author)
  • Uitterlinden, André G (author)
  • Brommage, Robert (author)
  • Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl (author)
  • Tobias, Jonathan H (author)
  • Rivadeneira, Fernando (author)
  • Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)

Related titles

  • In:PLoS genetics: Public Library of Science (PLoS)8:71553-7404

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view