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- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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- Damm, Henrik, et al.
(författare)
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Prevalence and morbidity of neck pain: a cross-sectional study of 3000 elderly men
- 2023
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Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe purpose of this study is to determine the prevalence and morbidity of neck pain with or without cervical rhizopathy, upper extremity motor deficit and/or thoracolumbar pain in elderly men.MethodsWe conducted a cross-sectional questionnaire study of 3,000 community-dwelling older men with a mean age of 75.4 +/- 3.2 years (range 69-81) to determine if they had experienced neck pain with or without cervical rhizopathy/upper extremity motor deficit/thoracolumbar pain (yes/no) during the preceding 12 months, and if so, morbidity with the condition (no/minor/moderate/severe).ResultsAmong the participants, 865 (29%) reported they had experienced neck and 1,619 (54%) thoracolumbar pain. Among the men with neck pain, 59% had experienced only neck pain, 17% neck pain and cervical rhizopathy and 24% neck pain, rhizopathy and motor deficit. For men with only neck pain, the morbidity was severe in 13%, for men with neck pain and rhizopathy it was 24%, and for men with pain, rhizopathy and motor deficit it was 46% (p < 0.001). Among the men with neck pain, 23% had experienced only neck pain and no thoracolumbar pain; the remaining 77% had both neck and thoracolumbar pain. The morbidity was severe in 10% of the men with neck pain but no thoracolumbar pain and 30% in men with neck and thoracolumbar pain (p < 0.001).ConclusionNeck pain in elderly men is common but symptoms and morbidity vary. For men who only have neck pain, 1/8 rated their morbidity as severe, while almost half who also had cervical rhizopathy and motor deficit and almost 1/3 of those who also had thoracolumbar pain reported severe morbidity.
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- Mellstrom, D, et al.
(författare)
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Osteoporosis, metabolic aberrations, and increased risk for vertebral fractures after partial gastrectomy
- 1993
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Ingår i: Calcified Tissue International. - 1432-0827. ; 53:6, s. 370-377
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Tidskriftsartikel (refereegranskat)abstract
- A case-control study compared 129 men with earlier partial gastrectomy (operation during the period 1952-1961) with 216 men from a community-based population study. All were born 1910-1915 and the mean age was 72 years. Men with a previous partial gastrectomy had vertebral fractures in 19% compared with 4% (P < 0.01) in the control population. Bone mineral density (BMD) in the right calcaneus measured with dual energy photon absorptiometry was 20% lower in men with a Billroth II operation (P < 0.001) and 8% lower with a Billroth I operation (ns). In comparison with the controls, the men subjected to partial gastrectomy had higher serum concentrations of osteocalcin and alkaline phosphatase activity, a lower serum concentration of 25-hydroxyvitamin D (25OHD) and a lower body mass index (BMI). There were no difference in serum concentrations of free calcium, intact parathyroid hormone (PTH), or free thyroxine. The smoking prevalence was significantly higher in men with partial gastrectomy than in controls. Smokers had significantly lower serum concentrations of intact PTH and 25OHD than nonsmokers and also lower BMD and BMI. The relationships between intact PTH on one hand, and ionized calcium (inverse relationship) and osteocalcin (direct relationship) on the other were preserved in smokers, however. Gastroscopy was performed in 78 men with multiple biopsies in the gastric remnant and also in the small intestine. All but two subjects had chronic gastritis. Examination of sternal bone marrow smears showed that 40% of the Billroth-operated men lacked bone marrow reticular iron.(ABSTRACT TRUNCATED AT 250 WORDS)
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- Westerberg, Per-Anton, et al.
(författare)
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Variation in the klotho gene is not associated with mortality risk among elderly men in MR OS Sweden
- 2012
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 50:Suppl 1, s. S103-S104
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Polymorphisms in the Klotho (Kl) gene, which is central for vitamin D regulation by fibroblast growth factor 23 (FGF23), have been associated with longevity, coronary disease and stroke. The CC genotype of the single nucleotide polymorphism (SNP) rs577912 in the Kl-gene is associated with decreased Kl expression, as well as increased mortality in end stage renal disease. We examined if SNP in the Kl-gene was associated with mortality in the community derived cohort of 70 to 80 year old males of MrOS Sweden (N = 3014).High throughput genotyping of the KLOTHO SNPs was achieved by use of SequenomR MassEXTEND/Mass/ARRAY technology. 2738 subjects had a valid result for rs577912: CC 73.1% and CA + AA 26.9%. There were no differences in the serum levels of FGF23, phosphate, parathyroid hormone or renal function between genotypes CC and CA + AA. During a follow-up of a median of 4.5 years there were 337 deaths, 253 (12.6%) in the CC group and 84 (11.4%) in the CA + AA group. With log rank analysis there were no differences in mortality between the genotypes for all cause mortality (P = 0.39) or cardiovascular mortality (P = 0.60). None of the other SNPs in the Kl gene was associated with mortality in this cohort either.Conclusion:There is no association between the SNP rs577912 in the Kl-gene and mortality among elderly men.
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- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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