Jennifer S Gregory

University of Aberdeen | ABDN · Division of Applied Medicine

Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in...

Advances in image quality from modern dual-energy X-ray absorptiometry (DXA) scanners now allow near radiograph-like quality images at a low radiation dose. This opens potential new applications for the use of DXA scanners to study other musculoskeletal conditions, such as osteoarthritis, which is often investigated by visual assessment of radiogra...

After spinal cord injury (SCI), bone loss in the paralysed limbs progresses at variable rates. Decreases in bone mineral density (BMD) in the first year range from 1% (slow) to 40% (rapid). In chronic SCI, fragility fractures commonly occur around the knee, with significant associated morbidity. Osteoporosis treatments await full evaluation in SCI,...

Few methods exist to measure the progression of osteoarthritis (OA) or to identify people at high risk of developing OA. Striking radiographic changes include deformation of the femoral head and osteophyte growth, which are usually measured semiquantitatively following visual assessment. In this study, an active shape model (ASM) of the proximal fe...

Purpose: There is a continuing need to improve the prediction of hip fractures to identify those at highest risk, enabling cost-effective use of preventative therapies. Methods: The aim of this work was to validate an innovative imaging biomarker for hip fracture by modelling the shape and texture of the proximal femur assessed from dual energy...

Objective We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60–64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. Methods Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-repo...

Objective We aimed to create an imaging biomarker for knee shape using knee dual-energy x-ray absorptiometry (DXA) scans and investigate its potential association with subsequent total knee replacement (TKR), independently of radiographic features of knee osteoarthritis and established risk factors. Methods Using a 129-point statistical shape mode...

Objective: We developed a novel imaging biomarker derived from knee dual-energy x-ray absorptiometry (DXA) to predict subsequent total knee replacement (TKR). The biomarker is based on knee shape, determined through statistical shape modelling. It was developed and evaluated using data and scans from the UK Biobank cohort. Methods: Using a 129-poin...

Background: Hip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest. Methods: GWAS...

Objectives To examine the extent to which geometric parameters derived from dual-energy x-ray absorptiometry (DXA) scans in the UK Biobank (UKB) study are related to hip osteoarthritis (HOA) independently of sex, age and body size. Methods Femoral neck width (FNW), diameter of the femoral head (DFH) and hip axis length (HAL) were derived automatica...

Objective Minimum joint space width (mJSW) from 2-dimensional images provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and use them to (ii) examine causal effects of mJSW on hip osteoarthritis (HOA) risk. Methods GWAS meta-analysis o...

Objective To examine the genetic architecture of cam morphology using alpha angle (AA) as a proxy measure and conduct an AA genome‐wide association study (GWAS) followed by Mendelian randomization (MR) to evaluate its causal relationship with hip osteoarthritis (OA). Methods Observational analyses examined associations between AA measurements deri...

Osteophytes are distinctive radiographic features of osteo-arthritis (OA) in the form of small bone spurs protruding from joints that contribute significantly to symptoms. Identifying the genetic determinants of osteophytes would improve the understanding of their biological pathways and contributions to OA. To date, this has not been possible due...

Objectives To examine the genetic architecture of cam morphology, using alpha angle (AA) as a proxy measure, we conducted an AA genome wide association study (GWAS), followed by Mendelian randomisation (MR) to evaluate its causal relationship with hip osteoarthritis (HOA). Methods Observational analyses examined associations between AA derived fro...

The contribution of shape changes to hip osteoarthritis (HOA) remains unclear, as is the extent to which these vary according to HOA severity. In the present study, we used statistical shape modelling (SSM) to evaluate relationships between hip shape and HOA of different severities using UK Biobank DXA images. We performed a cross‐sectional study i...

Background/Aims Radiographic hip osteoarthritis (rHOA) is traditionally defined on hip x-rays, using subjective methods such as Kellgren-Lawrence scoring. Associations between subjective rHOA measures and symptoms are inconsistent. Applying digital tools to high-resolution dual-energy X-ray absorptiometry (DXA) scans, we aimed to develop a novel se...

Purpose: Exercise reduces pain and improves physical function inosteoarthritis (OA) patients with no negative effects on wet or imagingbiomarkers. Exercises with high strain magnitudes and rates are ben-eficial for bone health. High impact exercise generates high strainmagnitudes and rates required for an osteogenic response however, theeffects on...

The growing burden from osteoporosis and fragility fractures highlights a need to improve osteoporosis management across healthcare systems. Sub-optimal management of osteoporosis is an area suitable for digital health interventions. While fracture liaison services (FLSs) are proven to greatly improve care for people with osteoporosis, such service...

Objective Conventional scoring methods for radiographic hip osteoarthritis (rHOA) are subjective and show inconsistent relationships with clinical outcomes. To provide a more objective rHOA scoring method, we aimed to develop a semi-automated classifier based on dual-energy X-ray absorptiometry (DXA) images, and confirm its relationships with clini...

Objective It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method. Methods Hip DXAs were obtained from UK Biobank. A novel automated m...

Objectives To examine whether acetabular dysplasia (AD), cam and/or pincer morphology are associated with radiographic hip osteoarthritis (rHOA) and hip pain in UK Biobank (UKB) and, if so, what distribution of osteophytes is observed. Design Participants from UKB with a left hip dual-energy x-ray absorptiometry (DXA) scan had alpha angle (AA), la...

Introduction Microsoft HoloLens® is an augmented-reality headset which is increasingly used for surgical guidance. This headset allows the overlay of patient-specific virtual models obtained from medical images onto the patient’s body surface using automatic marker-based alignment. This can guide surgeons during certain surgical tasks, e.g. determi...

Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fr...

Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fr...

Objective The purpose of this study is to describe predictors of total hip replacement (THR) in community dwelling older adults. A better understanding of predictors of THR can aid in triaging patients and researching preventative strategies. Design At baseline, participants had assessment of radiographic OA and cam morphology (from pelvic radiogr...

Objective It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method. Methods Hip DXAs were obtained from UK Biobank. An automated method...

Emerging holographic headsets can be used to register patient-specific virtual models obtained from medical scans with the patient’s body. Maximising accuracy of the virtual models’ inclination angle and position (ideally, ≤ 2° and ≤ 2 mm, respectively, as in currently approved navigation systems) is vital for this application to be useful. This st...

Objective Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape. Methods Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (AL...

Objectives: Hip development is influenced by mechanical loading, but associations between prenatal loading and hip shape in later life remain unexplored. Methods: We examined associations between prenatal loading indicators (gestation length, oligohydramnios (OH) and breech) obtained from obstetric records and hip shape modes (HSMs) generated us...

Background: Lumbar disc degeneration (LDD) is a condition associated with recurrent low back pain (LBP). Knowledge regarding effective management is limited. As a step towards the identification of risk, prognostic or potentially modifiable factors in LDD patients, the aim of this study was to explore the hypothesis that intrinsic lumbar spine sha...

Background Anticholinergic burden (ACB) is a recognised risk factor for falls in older people; however, whether ACB in middle age predicts falls in later life is unknown. Methods We examined this association in the middle-aged women of the Aberdeen Prospective Osteoporosis Screening Study (APOSS). ACB was calculated at the second health visit (199...

Objective Statistical shape modelling (SSM) of hip dual-energy x-ray absorptiometry (DXA) scans has identified relationships between hip shape and radiographic hip OA (rHOA). We aimed to further elucidate shape characteristics related to rHOA by focusing on subregions identified from whole-hip shape models. Method SSM was applied to hip DXAs obtai...

Objective High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. Design A cohort with and without HBM (L1 and/or total hi...

Hip shape is an important determinant of hip osteoarthritis (OA), which occurs more commonly in women. However, it remains unclear to what extent differences in OA prevalence are attributed to sex differences in hip shape. Here, we explore sex differences in proximal femur shape in a cohort of adolescents. Hip morphology was quantified using hip DX...

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine fro...

Objectives: Responsive biomarkers are needed to assess the progression of OA and their lack has hampered previous clinical trials. Statistical shape modelling (SSM) from radiographic images identifies those at greatest risk of fast-progression or joint replacement, but its sensitivity to change has not previously been measured. This study evaluate...

(The American Journal of Human Genetics 105, 1222–1236; December 5, 2019) As a result of an error in the proof process for the originally published version of this article, the surname of author Andrew Skol was misspelled as “Andrew Sko,” and the surname of author Greta Sokoloff was misspelled as “Sokolof.” These errors have now been corrected in t...

Background Hip osteoarthritis (OA) commonly affects older adults and leads to high morbidity. There is no preventative treatment available and total hip replacement (THR) is offered for end stage disease. Known predictors of THR include pain and radiographic OA. Hip structure has also been shown to worsen hip OA and predict THR. A better understand...

Background: Hip osteoarthritis (OA) commonly affects older adults and leads to high morbidity. There is no preventative treatment available and total hip replacement (THR) is offered for end stage disease. Known predictors of THR include pain and radiographic OA. Hip structure has also been shown to worsen hip OA and predict THR. A better understan...

Muscle bulk in adult healthy humans is highly variable even after height, age, and sex are accounted for. Low muscle mass, due to fewer and/or smaller constituent muscle fibers, would exacerbate the impact of muscle loss occurring in aging or disease. Genetic variability substantially influences muscle mass differences, but causative genes remain l...

Objective: To examine the relationship between pubertal timing (using measures of height tempo) and proximal femur shape in a large adolescent cohort. Methods: Hip DXA scans were obtained in offspring from the Avon Longitudinal Study of Parents and Children. To quantify hip morphology, the images were analyzed using Shape software based on a 53-...

Bones are complex objects with considerable variation in the shape and structure often attributed to anatomical, environmental or genetic differences. In addition, bone shape has been of interest in relation to its associations with disease processes. Hip shape is an important determinant of hip osteoarthritis and osteoporotic hip fracture; however...

Purpose: Multiple predictors of hip replacement have been described, but whether they are independent of the current gold standard predictors (pain and radiographic hip OA) is unclear. Therefore, we aimed to describe predictors of total hip replacement (THR) independent of hip pain and radiographic measures of hip OA in a community dwelling sample...

Hip shape is an important determinant of hip osteoarthritis and osteoporotic hip fracture; however, little is known about its development in childhood and adolescence. While previous studies largely focused on individual geometrical indices of hip geometry such as neck-shaft angle or femoral neck width, statistical shape modelling offers the means...

Supporting Information S1.

The LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50...

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements, and, accordingly, earlier walking is associated with greater bone...

We aimed to examine whether back pain across adulthood was associated with spine shape at age 60–64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60–64 years. Cumulative exposure...

We aimed to report the first genome‐wide association study (GWAS) meta‐analysis of dual‐energy X‐ray absorptiometry (DXA)‐derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modelling using SHAPE software, from hip DXA scans in the Av...

The LG/J x SM/J advanced intercross line of mice ( LG x SM AIL ) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 5...

Muscle bulk in humans is highly variable even after accounting for differences in height, age and sex, hence the impact of aging-related muscle loss known as sarcopenia varies in a similar fashion. Although heritability estimates are 40-80%, only a small number of muscle mass affecting genes have been identified. In 95,545 genotyped individuals of...

This study investigated associations between measures of adiposity from age 36 and spine shape at 60–64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60–6...

Correlations between body composition measures at age 60–64. (PDF)

Associations of BMI and waist circumference across adulthood with spine modes. (PDF)

Objective To investigate whether hip shape contributes to osteoarthritis (OA) development, we investigated relationships between known OA susceptibility loci and hip shape in a population‐based cohort of peri‐menopausal women. Methods Hip shape was measured using Statistical Shape Modelling, on hip DXA scans from mothers in the Avon Longitudinal S...

Background Various hip shapes may be important as a risk factor for development and progression of knee osteoarthritis, due to the biomechanical link between the two joints. Objectives This study aims to identify the relationship between hip morphology and structural and clinical osteoarthritis outcomes in the knee over 10.7 years, in older-adults...

Objective: Predicting who will develop osteoarthritis, assessing how rapidly their disease will progress and monitoring early responses to treatment are key to the development of therapeutic agents able to treat this crippling disease and to their future clinical use. Statistical Shape Modelling (SSM) enables quantification of variations in multip...

The genetics underlying variation in health-related musculoskeletal phenotypes can be investigated in a mouse model. Quantitative trait loci (QTLs) affecting musculoskeletal traits in the LG/J and SM/J strain lineage remain to be refined and corroborated. The aim of this study was to map muscle and bone traits in males (n = 506) of the 50th filial...

Background Injury is an important risk factor for osteoarthritis (OA), a highly prevalent and disabling joint disease. Joint shape is linked to OA, but the interplay of injury and joint shape and their combined role in OA, particularly at the ankle, is not well known. Therefore, we explored cross-sectional associations between ankle shape and injur...

Objective: Statistical shape modeling (SSM) of radiographs has been used to explore relationships between altered joint shape and hip osteoarthritis (OA). We aimed to apply SSM to Dual-energy X-ray Absorptiometry (DXA) hip scans, and examine associations between resultant hip shape modes (HSMs), radiographic hip OA (RHOA), and hip pain, in a large...

Table S1. Unadjusted correlations between hip modes 1–10 and height, weight, BMI and total hip BMD, by sex. Table S2. Unadjusted correlations between spine modes 1–8 and height, weight, BMI and lumbar spine BMD, by sex. Table S3. Unadjusted correlations between hip modes (HM1–10) and spine modes (SM1–8) in (a) men and (b) women. Fig. S1. Effects...

Objective: To examine the associations of body mass index (BMI) across adulthood with hip shapes at age 60-64years. Methods: Up to 1633 men and women from the MRC National Survey of Health and Development with repeat measures of BMI across adulthood and posterior-anterior dual-energy X-ray absorptiometry bone mineral density images of the proxim...

The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition stat...