Citations 2
Body mass index and subsequent fracture risk: a meta-analysis to update FRAX
Harvey, Nicholas C. , Johansson, Helena, McCloskey, Eugène , Liu, Enwu , Åkesson, Kristina , Anderson, Fred, Bager, Cecilie L. , Christiansen, Claus, Cooper, Cyrus , Crandall, Carolyn , Cummings, Steven R. , Dawson‐Hughes, Bess , Eisman, John A. , Fujita, Yuki , Fujiwara, Saeko , Glüer, Claus‐Christian , Guðnason, Vilmundur , Hall, Jill, Huisman, Martijn , Iki, Masayuki , Ish‐Shalom, Sophia, Koromani, Fjorda , Kröger, Heikki , Esfahani, Zahra , McGuigan, Fiona E. , Mellström, Dan, Merlijn, Thomas , Nguyen, Tuan V., Ohlsson, Claes , Pasco, Julie A. , Rivadeneira, Fernando, Schei, Berit , Shiroma, Eric J. , Siggeirsdóttir, Kristín , Swart, Karin M. A. , Tamaki, Junko , Staa, Tjeerd van , Wareham, Nicholas J, Yoshimura, Noriko , Zwart, Marta , Kanis, John A, McCloskey, Eugene V , Åkesson, Kristina E , Biver, Emmanuel , Center, Jacqueline R , Cooper, Cyrus , Crandall, Carolyn J , Dawson-Hughes, Bess , Dufour, Alyssa B , Eisman, John A , Ferrari, Serge , Hans, Didier B. , Iki, Masayuki , Karlsson, Magnus K , Khosla, Sundeep , Kiel, Douglas P , Koromani, Fjorda , Kwok, Timothy , Lamy, Olivier , Larijani, Bagher , McGuigan, Fiona E A , Merlijn, Thomas , Ohlsson, Claes , Orwoll, Eric S , Simonsick, Eleanor Marie , Sund, Reijo , Szulc, Pawel , Tamaki, Junko , Wright, Nicole C , Zillikens, M. Carola , Lorentzon, Mattias , Leslie, William D , Azagra, Rafael , Beaudart, Charlotte , Bischoff‐Ferrari, Heike A. , Biver, Emmanuel , Bruyère, Olivier , Cauley, Jane A. , Chapurlat, Roland D , Silva, José António Pereira da , Díez‐Pérez, Adolfo , Elders, Petra J. M. , Ferrari, Serge , Goldshtein, Inbal , Goltzman, David , Hall, Jill, Hoff, Mari , Hollick, Rosemary J , Jones, Graeme , Khosla, Sundeep , Kiel, Douglas P. , Koh, Woon‐Puay , Kotowicz, Mark A. , Langhammer, Arnulf , Lippuner, Kurt , Nordström, Anna , Nordström, Peter , O’Neill, Terence W , Obermayer-Pietsch, Barbara Maria , Orwoll, Eric , Rivadeneira, Fernando , Schott, Anne‐Marie , Sornay‐Rendu, Elisabeth , Szulc, Paweł , Torgerson, David John , Schoor, Natasja M. van , Vila, Joan , Vandenput, Liesbeth , Lorentzon, Mattias , Leslie, William D. , Kanis, John A.
Journal of Bone and Mineral Research | August 12, 2025 | Volume: 40 | Issue: 10 | Pages: 1144-1155
Abstract The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: <18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.
Fine-mapping reveals four TMEM106B haplotypes associated with neurodegenerative risk and preserved cognition at extreme age
Salazar, Alex , Knoop, Lydian, Huisman, Martijn, Tijms, Betty M. , Vijverberg, Everard, Wijesekera, Sanduni, Hiltunen, Mikko, Damme, Markus, Petrucelli, Leonard , Dijkstra, Anke A. , Hulsman, Marc , Tijms, Betty M , Tesi, Niccoló , Schoor, Natasja M. van , Lee, Sven J. van der , Křížová, Jana , Reinders, Marcel J. T. , Holtman, Inge R. , Holstege, Henne H.
No container title available | February 6, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
ABSTRACT Genetic variation at the TMEM106B locus has been associated with Alzheimer’s disease (AD) and related neurodegenerative phenotypes, yet its haplotypic architecture remains incompletely resolved. We refined the genetic landscape of TMEM106B by integrating AD-GWAS summary statistics (∼978K individuals) with haplotype analyses in 5,873 Dutch genomes including AD-cases, age-matched controls, and cognitively healthy centenarians. In addition to the known linkage disequilibrium (LD) block defining risk and protective haplotypes characterized by the amino acid substitution at residue 185 (Threonine/Serine), we identify a second conditionally independent LD block. Together these form four haplotypes (T1-T4), with T3 strongly enriched in centenarians. Long-read whole-genome sequencing in 493 individuals reveals haplotype-linked structural variation and methylation patterns, including a ∼19 Kbp genomic rearrangement carried by T3. These findings indicate that the TMEM106B locus comprises multiple haplotypes defined by methylation patterns and structural variants, offering insights into GWAS associations with AD risk and preserved cognition at extreme age.