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- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 2. |
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| 3. |
- Moayyeri, Alireza, et al.
(författare)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Tidskriftsartikel (refereegranskat)abstract
- 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. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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| 4. |
- Dhonukshe-Rutten, Rosalie A M, et al.
(författare)
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Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents.
- 2005
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 44:6, s. 341-347
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cobalamin deficiency is prevalent in vegetarians and has been associated with increased risk of osteoporosis. AIM OF THE STUDY: To examine the association between cobalamin status and bone mineral density in adolescents formerly fed a macrobiotic diet and in their counterparts. METHODS: In this cross-sectional study bone mineral density (BMD) and bone mineral content (BMC) were determined by DEXA in 73 adolescents (9-15 y) who were fed a macrobiotic diet up to the age of 6 years followed by a lacto-(-ovo-) vegetarian or omnivorous diet. Data from 94 adolescents having consumed an omnivorous diet throughout their lives were used as controls. Serum concentrations of cobalamin, methylmalonic acid (MMA) and homocysteine were measured and calcium intake was assessed by questionnaire. Analysis of covariance (MANCOVA) was performed to calculate adjusted means for vitamin B12 and MMA for low and normal BMC and BMD groups. RESULTS: Serum cobalamin concentrations were significantly lower (geometric mean (GM) 246 pmol/L vs. 469 pmol/L) and MMA concentrations were significantly higher (GM 0.27 micromol/L vs. 0.16 micromol/L) in the formerly macrobiotic-fed adolescents compared to their counterparts. In the total study population, after adjusting for height, weight, bone area, percent lean body mass, age, puberty and calcium intake, serum MMA was significantly higher in subjects with a low BMD (p = 0.0003) than in subjects with a normal BMD. Vitamin B12 was significantly lower in the group with low BMD (p = 0.0035) or BMC (p = 0.0038) than in the group with normal BMD or BMC. When analyses were restricted to the group of formerly macrobiotic-fed adolescents, MMA concentration remained higher in the low BMD group compared to the normal BMD group. CONCLUSIONS: In adolescents, signs of an impaired cobalamin status, as judged by elevated concentrations of methylmalonic acid, were associated with low BMD. This was especially true in adolescents fed a macrobiotic diet during the first years of life, where cobalamin deficiency was more prominent.
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