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GWAS Study

Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study.

Nethander M, Coward E, Reimann E et al.

36260985 PubMed ID
GWAS Study Type
735354 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

NM
Nethander M
CE
Coward E
RE
Reimann E
GL
Grahnemo L
GM
Gabrielsen ME
WC
Wibom C
MR
Mägi R
FT
Funck-Brentano T
HM
Hoff M
LA
Langhammer A
PU
Pettersson-Kymmer U
HK
Hveem K
OC
Ohlsson C
Chapter II

Abstract

Summary of the research findings

Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer's disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.

11,516 European ancestry cases, 723,838 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

735354
Total Participants
GWAS
Study Type
No
Replicated
European
Ancestry
Sweden, Norway, Finland, U.K., Estonia
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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