| 2. |
- Pettersson-Kymmer, Ulrika, et al.
(författare)
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Genome-wide association study meta-analysis identifies the SOAT1/AXDND1 locus to be associated with hip and forearm fracture risk
- 2013
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Ingår i: Bone Abstracts.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Hip and forearm fractures are the two clinically most important non-vertebral fractures. Twin studies have demonstrated a high heritability of these fractures and the heritable component of fracture risk is largely independent of BMD. To identify common genetic variants associated with hip and forearm fractures, we performed a genome-wide association study (GWAS ~ 2.5 million SNPs) meta-analysis of two large fracture data sets within the well-characterized UFO cohort (UFO-hip; 1014 hip fractures and 862 controls, and UFO-forearm; 1060 forearm fractures and 1055 controls). All fractures were confirmed through radiographic reports. Replication was performed in the Women’s Health Initiative (WHI) cohort (1845 hip fractures verified by medical records and 2120 controls). We identified one SNP within the SOAT1/AXDND1 locus (1q25.2) that was associated with fracture risk at genome wide significance (OR per allele=1.33; P=3.1×10−8) in the UFO discovery meta-analysis. This SNP was associated with fracture risk both in the WHI replication cohort (OR 1.16, P=2.1×10−3) and in the combined analyses comprising 7956 subjects (3919 cases and 4037 controls; OR=1.24, P=5.6×10−10). However, it was not associated with BMD or biochemical bone markers, suggesting that its association with fractures is BMD-independent. A genetic score (GS), including information from 63 SNPs earlier shown to be reproducibly associated with BMD, was significantly associated with both hip (P=7.9×10−4) and forearm (P=8.6×10−5) fractures. Models including both the SNP in the SOAT1/AXDND1 locus and the GS demonstrated that the impact of the SNP in the SOAT1/AXDND1 locus on fracture risk was independent of the BMD-associated GS. In summary, both a BMD-associated GS and a non-BMD associated genetic variant in the SOAT1/AXDND1 locus are associated with hip and forearm fractures.
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| 3. |
- Söderberg, Stefan, et al.
(författare)
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Leptin predicts independently a first-ever STEMI in men, data from a large prospective nested case-referent study
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: The adipocyte derived hormone leptin could be a mediator between obesity and increased risk for cardiovascular disease (CVD), asleptin has been linked to the atherosclerotic process. We hypothesised that leptin predicted independently a myocardial infarction (MI).Methods: A prospective nested case-referent study was set up within the framework of the Northern Sweden MONitoring of Trends and Determinants in CArdiovascular Diseases (MONICA) project, the Västerbotten Intervention Program (VIP), and the Mammary Screening Program (MSP). Subjects (n=564, 40% women) with a first-ever acute MI that had participated in one of these surveys prior to the MI were selected. Age, sex, survey and location matched referents (n=1082, 40% women) were selected within the surveys. Leptin was measured instored plasma. Conditional logistic regression was used to determine the risk for MI. Type of MI (STEMI and NSTEMI) was classified according to Minnesota codes.Results: The time period between survey and event was 3.9 years (interquartile range 3.6), and 51% of the cases had STEMI, 29% had NSTEMI, and 21% were unclassified. Male and female cases had higher levels of leptin (5.0 vs. 4.1 ng/mL, p<0.001 and 15.4 vs. 14.0 ng/mL, p=0.03), compared to referents. High leptin levels predicted MIindependently in men (OR 2.17 [1.32-3.54], ptrend<0.001), but not inwomen (OR 1.10 [0.55-2.18], ptrend=0.05). The risk related to leptin inmen was seen for STEMI in particular.Conclusions: High leptin predicts first–ever fatal and non–fatal MI, notably with a gender and MI-type difference. Leptin may affect theatherosclerotic process differentially in men and women and may promote plaque rupture and thrombus formation in larger coronary vessels.
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