Unveiling the mysteries of the genetics of osteoporosis

Alonso, Nerea; Ralston, Stuart H.

doi:10.1007/s40618-014-0149-7

Cited by 21 publications

(13 citation statements)

References 76 publications

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“…Many advances have been made in defining the genetic determinants of BMD and fractures through large-scale GWAS, genome sequencing studies and linkage studies in rare bone diseases 32. For example, linkage studies have shown that loss-of-function and gain-of-function variants in LRP5 cause early onset osteoporosis33 and high bone mass,34 respectively, whereas loss of function mutations affecting SOST and LRP4 have been identified as causes of high bone mass and osteosclerosis 35 36.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density

et al. 2017

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Objectives To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. Methods Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. Results A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10−9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. Conclusion We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density

et al. 2017

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“…Упродовж останніх років акцентується увага на значенні вітаміну D як імунного модулятора. Вітамін D проявляє свій ефект шляхом зв'язування з рецептором вітаміну D (VDR) і активації VDR-чутливих генів [3].…”

Section: вступunclassified

Частота Автоімунного Тиреоїдиту В Жінок На Тлі Гіповітамінозу D

Pankiv

2021

Mìžnarodnij endokrinologìčnij žurnal

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Резюме. Актуальність. Отримані на сьогодні результати численних наукових досліджень підтверджують багатогранний вплив вітаміну D на різні органи і системи людського організму. Тому дефіцит або недостатність вищезгаданого вітаміну набуває значущості предиктора розвитку широкого спектра патологічних станів. Мета дослідження: встановити взаємозв'язок між частотою автоімунного тиреоїдиту і дефіцитом вітаміну D. Матеріали та методи. Дослідження здійснене за методом «випадок -контроль». У дослідження включено 376 жінок, з яких у 52 відзначався нормальний вміст вітаміну D в крові, а у 324 -недостатність або дефіцит вітаміну D. Усім обстеженим проведено визначення рівня вітаміну D у сироватці крові, тиреотропного гормона, вільного тироксину, паратгормона, а також антитіл до тиреоїдної пероксидази. Результати. Демографічні характеристики обстежених жінок обох груп не відрізнялися (p > 0,05). Частота автоімунного тиреоїдиту виявилася вірогідно вищою в групі жінок із недостатністю та дефіцитом вітаміну D. Рівень антитіл до тиреоїдної пероксидази перебував у вірогідній кореляції з умістом вітаміну D. Висновки. Установлено взаємозв'язок між гіповітамінозом D та частотою автоімунного тиреоїдиту в жінок Карпатського регіону. Ключові слова: автоімунний тиреоїдит; дефіцит вітаміну D © «Міжнародний ендокринологічний журнал», 2017

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“…Excised skeletal elements such as individual femurs may also be analyzed. The majority of GWAS for loci controlling bone mass in humans have been based on these DXA measurements of BMD (9–11), and usually the focus is on either the lumbar spine or proximal femur (hip). In mice it is common to collect data for whole body BMD, as well as regions of interest encompassing several vertebrae or the entire femur.…”

Section: Genetic Loci Mapped For Bone Mineral Density In Micementioning

confidence: 99%

“…As a result, BMD is the most studied phenotype in bone from a forward genetics point of view. Indeed, in humans both common and rare genetic variants for this phenotype have been identified by GWAS, yet as is often the case with this type of study, the amount of variance collectively explained remains small (9–11). While these GWAS-identified loci have provided interesting and novel insights into the regulation of bone mass, BMD as a phenotype is an inadequate surrogate for bone strength or resistance to fracture, as we know from clinical studies that BMD is an imperfect predictor of fracture (12).…”

Section: Introductionmentioning

confidence: 99%

Genetics of aging bone

2016

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With aging, the skeleton experiences a number of changes, which include reductions in mass and changes in matrix composition, leading to fragility and ultimately an increase of fracture risk. A number of aspects of bone physiology are controlled by genetic factors, including peak bone mass, bone shape, and composition; however, forward genetic studies in humans have largely concentrated on clinically available measures such as bone mineral density (BMD). Forward genetic studies in rodents have also heavily focused on BMD; however, investigations of direct measures of bone strength, size, and shape have also been conducted. Overwhelmingly, these studies of the genetics of bone strength have identified loci that modulate strength via influencing bone size, and may not impact the matrix material properties of bone. Many of the rodent forward genetic studies lacked sufficient mapping resolution for candidate gene identification; however, newer studies using genetic mapping populations such as Advanced Intercrosses and the Collaborative Cross appear to have overcome this issue and show promise for future studies. The majority of the genetic mapping studies conducted to date have focused on younger animals and thus an understanding of the genetic control of age-related bone loss represents a key gap in knowledge.

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Unveiling the mysteries of the genetics of osteoporosis

Cited by 21 publications

References 76 publications

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density

Частота Автоімунного Тиреоїдиту В Жінок На Тлі Гіповітамінозу D

Genetics of aging bone

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