Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.
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SUBMITTER: Moayyeri A
PROVIDER: S-EPMC4038791 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
Publications
Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.
Moayyeri Alireza A Hsu Yi-Hsiang YH Karasik David D Estrada Karol K Xiao Su-Mei SM Nielson Carrie C Srikanth Priya P Giroux Sylvie S Wilson Scott G SG Zheng Hou-Feng HF Smith Albert V AV Pye Stephen R SR Leo Paul J PJ Teumer Alexander A Hwang Joo-Yeon JY Ohlsson Claes C McGuigan Fiona F Minster Ryan L RL Hayward Caroline C Olmos José M JM Lyytikäinen Leo-Pekka LP Lewis Joshua R JR Swart Karin M A KM Masi Laura L Oldmeadow Chris C Holliday Elizabeth G EG Cheng Sulin S van Schoor Natasja M NM Harvey Nicholas C NC Kruk Marcin M del Greco M Fabiola F Igl Wilmar W Trummer Olivia O Grigoriou Efi E Luben Robert R Liu Ching-Ti CT Zhou Yanhua Y Oei Ling L Medina-Gomez Carolina C Zmuda Joseph J Tranah Greg G Brown Suzanne J SJ Williams Frances M FM Soranzo Nicole N Jakobsdottir Johanna J Siggeirsdottir Kristin K Holliday Kate L KL Hannemann Anke A Go Min Jin MJ Garcia Melissa M Polasek Ozren O Laaksonen Marika M Zhu Kun K Enneman Anke W AW McEvoy Mark M Peel Roseanne R Sham Pak Chung PC Jaworski Maciej M Johansson Åsa Å Hicks Andrew A AA Pludowski Pawel P Scott Rodney R Dhonukshe-Rutten Rosalie A M RA van der Velde Nathalie N Kähönen Mika M Viikari Jorma S JS Sievänen Harri H Raitakari Olli T OT González-Macías Jesús J Hernández Jose L JL Mellström Dan D Ljunggren Osten O Cho Yoon Shin YS Völker Uwe U Nauck Matthias M Homuth Georg G Völzke Henry H Haring Robin R Brown Matthew A MA McCloskey Eugene E Nicholson Geoffrey C GC Eastell Richard R Eisman John A JA Jones Graeme G Reid Ian R IR Dennison Elaine M EM Wark John J Boonen Steven S Vanderschueren Dirk D Wu Frederick C W FC Aspelund Thor T Richards J Brent JB Bauer Doug D Hofman Albert A Khaw Kay-Tee KT Dedoussis George G Obermayer-Pietsch Barbara B Gyllensten Ulf U Pramstaller Peter P PP Lorenc Roman S RS Cooper Cyrus C Kung Annie Wai Chee AW Lips Paul P Alen Markku M Attia John J Brandi Maria Luisa ML de Groot Lisette C P G M LC Lehtimäki Terho T Riancho José A JA Campbell Harry H Liu Yongmei Y Harris Tamara B TB Akesson Kristina K Karlsson Magnus M Lee Jong-Young JY Wallaschofski Henri H Duncan Emma L EL O'Neill Terence W TW Gudnason Vilmundur V Spector Timothy D TD Rousseau François F Orwoll Eric E Cummings Steven R SR Wareham Nick J NJ Rivadeneira Fernando F Uitterlinden Andre G AG Prince Richard L RL Kiel Douglas P DP Reeve Jonathan J Kaptoge Stephen K SK
Human molecular genetics 20140114 11
Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independ ...[more]
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| S-EPMC6391516 | biostudies-literature
Project description:Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10(-8) as significant.Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6). Among migraineurs with aura rs7698623 in MEPE (OR?=?6.37; 95% CI 3.15-12.90; p?=?2.7×10(-7)) and rs4975709 in IRX4 (OR?=?5.06; 95% CI 2.66-9.62; p?=?7.7×10(-7)) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR?=?3.05; 95% CI 1.98-4.69; p?=?4.3×10(-7)), and the intergenic rs1406961 with CVD death (OR?=?12.33; 95% CI 4.62-32.87; p?=?5.2×10(-7)). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR?=?4.67; 95% CI 2.53-8.62; p?=?8.0×10(-7)).Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research.
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Project description:RationaleEmphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe-predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown.ObjectivesTo identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin-deficient smokers.MethodsA total of 11,532 subjects with complete genotype and computed tomography densitometry data in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]; non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), and GenKOLS (Genetics of Chronic Obstructive Lung Disease) studies were analyzed. Two computed tomography scan emphysema distribution measures (difference between upper-third and lower-third emphysema; ratio of upper-third to lower-third emphysema) were tested for genetic associations in all study subjects. Separate analyses in each study population were followed by a fixed effect metaanalysis. Single-nucleotide polymorphism-, gene-, and pathway-based approaches were used. In silico functional evaluation was also performed.Measurements and main resultsWe identified five loci associated with emphysema distribution at genome-wide significance. These loci included two previously reported associations with COPD susceptibility (4q31 near HHIP and 15q25 near CHRNA5) and three new associations near SOWAHB, TRAPPC9, and KIAA1462. Gene set analysis and in silico functional evaluation revealed pathways and cell types that may potentially contribute to the pathogenesis of emphysema distribution.ConclusionsThis multicohort genome-wide association study identified new genomic loci associated with differential emphysematous destruction throughout the lungs. These findings may point to new biologic pathways on which to expand diagnostic and therapeutic approaches in chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).
| S-EPMC5363968 | biostudies-literature
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