Body-shape trajectories and their genetic variance component in Gilthead seabream (Sparus aurata L.).

The phenotype of juvenile fish is closely associated with the adult phenotype, thus consisting an important quality trait for reared fish stocks. In this study, we estimated the correlation between the juvenile and adult body-shape in Gilthead seabream, and examined the genetic basis of the ontogenetic trajectories. The body shape of 959 pit-tagged fish was periodically examined during the juvenile-to-adult period. Individual shape ontogenetic trajectories were studied in respect to the initial (juvenile) and final (adult) phenotypes, as well as to the rate that adult phenotype is attained (phenotypic integration rate). We found that the juvenile body-shape presented a rapid change up to 192.7 ± 1.9 mm standard length, followed by a phenotypically stable period (plateau). Depending on the shape component considered, body-shape correlations between juvenile and adult stages ranged from 0.22 to 0.76. Heritability estimates (h2) of the final phenotype ranged from 0.370 ± 0.077 to 0.511 ± 0.089, whereas h2 for the phenotypic integration rate was 0.173 ± 0.062. To our knowledge, this is the first study demonstrating that the variance of the ontogenetic trajectories has a substantial additive genetic component. Results are discussed in respect to their potential use in selective breeding programs of Gilthead seabream.

GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer.

Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region-specific associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants, illustrating the importance of adjusting correctly for height.

Deconstructing and reconstructing joint hypermobility on an evo-devo perspective.

Joint hypermobility is a common characteristic in humans. Its non-casual association with various musculoskeletal complaints is known and currently defined "the spectrum". It includes hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). hEDS is recognized by a set of descriptive criteria, while HSD is the background diagnosis for individuals not fulfilling these criteria. Little is known about the aetiopathogenesis of the spectrum. It may be interpreted as a complex trait according to the integration model. Particularly, the spectrum is common in the general population, affects morphology, presents extreme clinical variability and is characterized by marked sex bias without a clear Mendelian or hormonal explanation. Joint hypermobility and the other hEDS systemic criteria are intended as qualitative derivatives of continuous traits of normal morphological variability. The need for a minimum set of criteria for hEDS diagnosis implies a tendency to co-vary of these underlying continuous traits. In evolutionary biology, such a co-variation (i.e. integration) is driven by multiple forces, including genetic, developmental, functional and environmental/acquired interactors. The aetiopathogenesis of the spectrum may be resolved by a deeper understanding of phenotypic variability, which superimposes on normal morphological variability.

Enlightenment about using TCM constitutions for individualized medicine and construction of Chinese-style precision medicine: research progress with TCM constitutions.

TCM constitution is a new branch of TCM. It provides enlightenment on individualized medicine, including the development of new models of individualized research based on nine constitutions, the acquisition of comprehensive health information for individuals, and establishment of a consistent individualized diagnosis and treatment system. Further, we propose a Chinese-style "precision medicine" based on individualization using the TCM constitutions.

Drivers and dynamics of a massive adaptive radiation in cichlid fishes.

Adaptive radiation is the likely source of much of the ecological and morphological diversity of life1-4. How adaptive radiations proceed and what determines their extent remains unclear in most cases1,4. Here we report the in-depth examination of the spectacular adaptive radiation of cichlid fishes in Lake Tanganyika. On the basis of whole-genome phylogenetic analyses, multivariate morphological measurements of three ecologically relevant trait complexes (body shape, upper oral jaw morphology and lower pharyngeal jaw shape), scoring of pigmentation patterns and approximations of the ecology of nearly all of the approximately 240 cichlid species endemic to Lake Tanganyika, we show that the radiation occurred within the confines of the lake and that morphological diversification proceeded in consecutive trait-specific pulses of rapid morphospace expansion. We provide empirical support for two theoretical predictions of how adaptive radiations proceed, the 'early-burst' scenario1,5 (for body shape) and the stages model1,6,7 (for all traits investigated). Through the analysis of two genomes per species and by taking advantage of the uneven distribution of species in subclades of the radiation, we further show that species richness scales positively with per-individual heterozygosity, but is not correlated with transposable element content, number of gene duplications or genome-wide levels of selection in coding sequences.

Genetics of somatotype and physical fitness in children and adolescents.

OBJECTIVES: To analyze the influence of genetic and environmental factors on the variation in somatotype, physical fitness, and their mutual associations. METHODS: Twins from 214 pairs (87 monozygotic) of the Autonomous Region of Madeira, Portugal, from 3 to 18 years of age (51% girls) were assessed in anthropometry and physical fitness tests. We estimated endomorphy, mesomorphy, and ectomorphy based on anthropometric measures and physical fitness using the Eurofit test battery. Two age categories were analyzed: children (3-11 years) and adolescents (12-18 years). Genetic and environmental variations were estimated using quantitative genetic twin modeling. RESULTS: No genetic sex differences were found, thus boys and girls were pooled in all genetic analyses. Heritability estimates were high for somatotype (a2  = 0.80-0.93), physical fitness traits (a2  = 0.67-0.83), and largely similar in children and adolescents. Positive correlations were found for ectomorphy with motor ability and cardiorespiratory endurance as well as for endomorphy and mesomorphy with muscular strength (r = 0.25-0.37). In contrast, negative associations were found for ectomorphy with muscular strength, as well as for endomorphy and mesomorphy with motor ability and cardiorespiratory endurance (-0.46 to -0.26). Twin modeling indicated that these associations were explained mostly by genetic factors in common to the two associated traits (84% or more). CONCLUSIONS: Associations between somatotype and physical fitness tests are mainly explained by common genetic background in children and adolescents. Therefore, interventions in youth should consider that a child's performance in physical fitness tests partly reflects their inherited physique.

Grupos de la constitución del cuerpo. en mujeres kirguisas / Groups of the body constitution in kyrgyz women

Introduction. It should be considered that the body constitution which is widely used in the preventive and clinical medicine, leaves an imprint on the body mass index. The objective of this work is to study the features of body mass index and fat body mass in females of different constitutional and age groups. Materials and Methods. Using the method of complex anthropometry and bioimpedancemetry ("Medass"), we have also studied the physical status of 580 ethnic Kyrgyz women living in Osh, Kyrgyzstan and its surroundings. Statistical data processing included the calculation of arithmetic mean and error, as well as the minimum and maximum of each indicator (variation amplitude). The significance of difference was assessed by Student's t-test. Results. The body length and weight and, accordingly, the body mass index, significantly depend on the type of body constitution. The absolute fat mass is also unequal in women of different constitutional groups. The minimum and maximum of the absolute and percentage fat mass in women of the period of adulthood II with different body constitutions are, in general, more than in juvenile period. Conclusion. The obtained results can be used to develop measures aimed at the timely detection of overweight and obesity as well as for the implementation of measures to prevent alimentary-related diseases in juvenile and adulthood period. Somatometric assessment of the physical development can be used in the dynamic monitoring of health status in organized groups: in educational institutions, youth sports schools, enterprises.

Genetic correlations between methane production and fertility, health, and body type traits in Danish Holstein cows.

Our aim was to investigate the genetic correlations between CH4 production and body conformation, fertility, and health traits in dairy cows. Data were collected from 10 commercial Holstein herds in Denmark, including 5,758 cows with records for body conformation traits, 7,390 for fertility traits, 7,439 for health traits, and 1,397 with individual CH4 measurements. Methane production was measured during milking in automatic milking systems, using a sniffer approach. Correlations between CH4 and several different traits were estimated. These traits were interval between calving and first insemination, interval between first and last insemination, number of inseminations, udder diseases, other diseases, height, body depth, chest width, dairy character, top line, and body condition score. Bivariate linear models were used to estimate the genetic parameters within and between CH4 and the other traits. In general, the genetic correlations between CH4 and the traits investigated were low. The heritability of CH4 was 0.25, and ranged from 0.02 to 0.07 for fertility and health traits, and from 0.17 to 0.74 for body conformation traits. Further research with a larger data set should be performed to more accurately establish how CH4 relates to fertility, health, and body conformation traits in dairy cattle. This will be useful in the design of future breeding goals that consider the production of CH4.

Phenotype analysis of congenital and neurodevelopmental disorders in the next generation sequencing era.

The designation, phenotype, was proposed as a term by Wilhelm Johannsen in 1909. The word is derived from the Greek, phano (showing) and typo (type), phanotypos. Phenotype has become a widely recognized term, even outside of the genetics community, in recent years with the ongoing identification of human disease genes. The term has been defined as the observable constitution of an organism, but sometimes refers to a condition when a person has a particular clinical presentation. Analysis of phenotype is a timely theme because advances in the understanding of the genetic basis of human disease and the emergence of next generation sequencing have spurred a renewed interest in phenotype and the proposal to establish a "Human Phenome Project." This article summarizes the principles of phenotype analysis that are important in medical genetics and describes approaches to comprehensive phenotype analysis in the investigation of patients with human disorders. I discuss the various elements related to disease phenotypes and highlight neurofibromatosis type 1 and the Elements of Morphology Project as illustrations of the principles. In recent years, the notion of "deep phenotyping" has emerged. Currently there are now a number of proposed strategies and resources to approach this concept. Not since the 1960s and 1970s has there been such an exciting time in the history of medicine surrounding the analysis of phenotype in genetic disorders.

Quantitative genetic analysis of the body composition and blood pressure association in two ethnically diverse populations.

OBJECTIVES: The major aim of this study was to conduct comparative quantitative-genetic analysis of the body composition (BCP) and somatotype (STP) variation, as well as their correlations with blood pressure (BP) in two ethnically, culturally and geographically different populations: Santhal, indigenous ethnic group from India and Chuvash, indigenous population from Russia. MATERIALS AND METHODS: Correspondently two pedigree-based samples were collected from 1,262 Santhal and1,558 Chuvash individuals, respectively. At the first stage of the study, descriptive statistics and a series of univariate regression analyses were calculated. Finally, multiple and multivariate regression (MMR) analyses, with BP measurements as dependent variables and age, sex, BCP and STP as independent variables were carried out in each sample separately. The significant and independent covariates of BP were identified and used for re-examination in pedigree-based variance decomposition analysis. RESULTS AND DISCUSSION: Despite clear and significant differences between the populations in BCP/STP, both Santhal and Chuvash were found to be predominantly mesomorphic irrespective of their sex. According to MMR analyses variation of BP significantly depended on age and mesomorphic component in both samples, and in addition on sex, ectomorphy and fat mass index in Santhal and on fat free mass index in Chuvash samples, respectively. Additive genetic component contributes to a substantial proportion of blood pressure and body composition variance. Variance component analysis in addition to above mentioned results suggests that additive genetic factors influence BP and BCP/STP associations significantly.

The obesity-risk variant of FTO is inversely related with the So-Eum constitutional type: genome-wide association and replication analyses.

BACKGROUND: Body constitutional types described in the traditional Korean medicine system, Sasang constitutional medicine, are heritable, as has been revealed by twin and family studies. Thus, individuals with the same constitution type usually have similar pathophysiological and psychological traits. In several recent genome-wide association (GWA) analyses performed to identify constitution-associated variants, the association signals were not replicated due to small sample size and dissimilar, non-objective methods for classification of the constitutional types. METHODS: We conducted GWA analysis and followed replication analysis in two large populations (5,490 subjects: 3,810 subjects at discovery stage and 1,680 subjects at replication stage) to identify the replicable constitution-associated variants, wherein subjects with the highest tertile of constitution probability values versus the reference with the lowest tertile of the values obtained from a recently developed constitution analysis tool were compared. RESULTS: We found that the obesity-risk variant in intron 1 of the fat mass and obesity-associated (FTO) gene was replicably inversely associated with the So-Eum (SE) type, characterized by reduced appetite, slim body, and cautious personality (rs7193144 in combined samples: odds ratio = 0.729, p = 1.47 × 10(-7)), and substantial association signal remained after controlling for body mass index (BMI). In contrast, the association of the variant with the Tae-Eum type, characterized by high body mass, disappeared after controlling BMI. CONCLUSIONS: In summary, the obesity-risk variant in FTO intron 1 was inversely associated with the SE type, independent of BMI, which corresponded well with the characteristics of the SE type, such as the lowest body mass and lowest susceptibility to metabolic disorders among the constitutional types. Therefore, the obesity-risk variant of FTO associated with body mass increase might be involved in the determination of body constitution type.

Somatotype tendency in Chilean adolescents from Valparaíso: review from 1979 to 2011 / Tendencia del somatotipo en adolescentes chilenos de Valparaíso: revisión de 1979 al 2011

Introduction: A good tool to determine the biotype of growing and developing subjects that has been observed is the somatotype (ST). Objetive: This research study aims to describe the ST tendency in Chilean adolescents along the years. Methods: The bibliographic review was carried out using data from Medline, ISI Web of Knowledge, and SciELO. The key words used for the search were: somatotype, somatotyping, adolescent (in English and Spanish). The selected articles must describe ST in Chilean adolescents between 15 and 18 years of age. The graphic representation was made through a somatochart and the series ST. To analyze the trajectory of the ST, the moving average method was used (SM), and the tendency line (lineal; TL), which expresses the data direction and projection. Results: Eight articles complied with the inclusion criteria. Samples of students between 1979 and 2011 from the Regions of Valparaíso, Araucanía, and the Metropolitan region of Chile were reported. All studies correspond to transversal samples. The authors cite and/or describe the Heath-Carter anthropometric methods to assess the ST. The results showed positive TL for the endomorph component in all ages and genders. The mesomorph component maintained in male, unlike the female’s component, which was negative except for the one at 18 years old. SM trajectory describes a regularity of the mesomorphic endomorph profile in female, yet with an increase in the endomorphy. In male, a change was observed from an ectomorphic mesomorph to endomorphic mesomorph. Conclusions: This progressive rise of the adipose component in both genders increases the risk of suffering non-communicable diseases (AU)

Introducción: Se ha observado que el somatotipo (ST) antropométrico es un buen método para determinar el biotipo de sujetos en crecimiento y desarrollo. Objetivo: Describir la tendencia del ST en adolescentes chilenos a lo largo de los años. Métodos: La búsqueda bibliográfica se realizó en bases de datos Medline, ISI Web of Knowlegde y SciELO. Las palabras claves utilizadas para la búsqueda fueron: somatotipo, adolescente (tanto en inglés como español). Los artículos seleccionados debían describir el ST en adolescentes chilenos de 15 a 18 años de edad. Para la representación gráfica se utilizó la somatocarta y el ST de series, para el análisis de la trayectoria del ST se ocupó el mé- todo de medias móviles (SM) y líneas de tendencia (TL). Resultados: Los artículos que cumplieron con los criterios de inclusión fueron ocho. Las muestras de estudiantes se describen desde los años 1979 hasta el 2011, en las regiones de Valparaíso, Araucanía y Metropolitana. Todos los estudios corresponden a estudios transversales. Los autores citan y/o describen el método antropométrico de Healh-Carter para evaluar el ST. Se registraron TL positivas para el componente endomorfo en todas las edades y géneros, el componente mesomorfo se mantuvo en hombres, no así en mujeres que fue negativo a excepción de los 18 años. La trayectoria SM describe una persistencia del perfil meso-endomorfo en mujeres, pero con aumento de la endomorfía. En hombres se observó el cambio de un perfil ecto-mesomorfo hacia uno meso-endomorfo. Conclusiones: Este aumento progresivo del componente endomórfico en ambos géneros incrementa el riesgo de padecer enfermedades crónicas no trasmisibles (AU)

Transcriptome profile analysis of adipose tissues from fat and short-tailed sheep.

Recent studies in domestic animals have used RNA-seq to explore the transcriptome of different tissues in a limited number of individuals. In the present study, de novo transcriptome sequencing was used to compare sheep adipose tissue transcriptome profiles between a fat-tailed breed (Kazak sheep; KS) and a short-tailed (Tibetan sheep; TS). The RNA-seq data from these two groups revealed that 646 genes were differentially expressed between the KS and TS groups, including 280 up-regulated and 366 down-regulated genes. We identified genes relevant to fat metabolism in adipose tissues, including two top genes with the largest fold change (NELL1 and FMO3). Pathway analysis revealed that the differentially expressed genes between the KS and TS breeds belong to fatty acid metabolism relevant pathways (e.g. fat digestion and absorption, glycine, serine, and threonine metabolism) and cell junction-related pathways (e.g. cell adhesion molecules) which contribute to fat deposition. This work highlighted potential genes and gene networks that affect fat deposition and meat quality in sheep.

The relationship of metabolic syndrome and constitutional medicine for the prediction of cardiovascular disease.

UNLABELLED: The concept of Sasang Constitutional Medicine (SCM) has been in existence in Traditional Korean Medicine for more than 100 years. SCM consists of 4 different types; So-Eum (SE), So-Yang (SY), Tae-Eum (TE), and Tae-Yang (TY). In Western medicine, it is more like stratifying individuals according to phenotypic expression. It is of great importance that the Sasang constitution type be evaluated accurately and recognized by the medical communities for prevention, early diagnosis and treatment of cardiovascular diseases (CVD). SUBJECTS AND METHODS: From the Ansung-Ansan prospective cohort study, 10,038 participants were recruited from years 2001-2002. Of 10,038 original participants, 3022 subjects underwent Sasang Constitutional Type (SCT) evaluation. The Cox proportional hazard model was used to predict CVD during the ten year follow-up period. RESULTS: Of 3022 participants, SCT classified into 364 (12%) SE, 1053 (34.8%) SY, 1605 (53.1%) TE, and no TY. Three hundred seventy nine (16%) newly developed CVD during the following period, yielding 10-year cumulative incidence of 160/1000 person. The frequency of CVD within three SCT without metabolic syndrome (MetS) shows 13.4% in SE, 13.6% in SY, and 14.3% in TE, respectively (p=NS). The CVD events were significantly different among the types when MetS was present. The demographic and clinical characteristics revealed the TE group was significantly older, more obese, higher blood pressure, glucose values, and lipid profiles levels. The frequency of MetS and type 2 diabetes mellitus (T2DM) was also higher in TE type than either SE and SY types (all p<0.001). The Cox proportional hazard analysis revealed age, female gender, rural residence, higher ALT level, and lower beta-cell function remain as an independent risk factor, as well as SY with MetS (RR=1.838 (95% CI 1.23-2.74), p=0.003). Furthermore, 10 year CVD survival rate was 86.4% in no MetS group, 83.4% in TE, 79.6% in SE, and 76.4% in SY all with MetS (p<0.001). CONCLUSIONS: The findings from this study suggest MetS increases risk for CVD in certain physical conditions like SY type. Therefore, we would like to suggest that SCT is a strong indicator for CVD.

Novel polymorphisms of the APOA2 gene and its promoter region affect body traits in cattle.

Apolipoprotein A-II (APOA2) is one of the major constituents of high-density lipoprotein and plays a critical role in lipid metabolism and obesity. However, similar research for the bovine APOA2 gene is lacking. In this study, polymorphisms of the bovine APOA2 gene and its promoter region were detected in 1021 cows from four breeds by sequencing and PCR-RFLP methods. Totally, we detected six novel mutations which included one mutation in the promoter region, two mutations in the exons and three mutations in the introns. There were four polymorphisms within APOA2 gene were analyzed. The allele A, T, T and G frequencies of the four loci were predominant in the four breeds when in separate or combinations analysis which suggested cows with those alleles to be more adapted to the steppe environment. The association analysis indicated three SVs in Nangyang cows, two SVs in Qinchun cows and the 9 haplotypes in Nangyang cows were significantly associated with body traits (P<0.05 or P<0.01). The results of this study suggested the bovine APOA2 gene may be a strong candidate gene for body traits in the cattle breeding program.

Reestructuraciones compatibles con un fenotipo normal detectadas en diagnóstico prenatal / Chromosome reorganizations compatible with a normal phenotype detected during a prenatal diagnosis

Introducción. Se conocen numerosas reestructuraciones cromosómicas compatibles con un fenotipo normal, principalmente algunos cromosomas marcadores sin contenido genéticamente relevante y heteromorfismos cromosómicos. Material y métodos. Estudio retrospectivo de 20.098 casos prenatales. Resultados. Se han detectado 24/17.784 casos (0,13%) de pequeños cromosomas marcadores (SMC) en líquido amniótico, 8/2.223 (0,36%) en vellosidad corial y 31/20.007 (0,15%) reestructuraciones estructurales clasificadas como heteromorfismos. Conclusiones. Se proponen guías de actuación basándose en nuestra experiencia y la bibliografía existente(AU)

Introduction. Many chromosome reorganizations compatible with a normal phenotype are known, mainly some marker chromosomes with no genetically relevant content or chromosomal heteromorphisms. Material and methods. Retrospective study of 20,098 prenatal cases. Results. We detected 24/17,784 cases (0.13%) of small marker chromosomes (SMCs) in amniotic fluid, 8/2223 (0.36%) in chorionic villus, and 31/20,007 (0.15%) structural reorganizations classified as heteromorphisms. Conclusions. Clinical practice guidelines are proposed based on our experience and the literature(AU)

Development of an integrated Sasang constitution diagnosis method using face, body shape, voice, and questionnaire information.

BACKGROUND: Sasang constitutional medicine (SCM) is a unique form of traditional Korean medicine that divides human beings into four constitutional types (Tae-Yang: TY, Tae-Eum: TE, So-Yang: SY, and So-Eum: SE), which differ in inherited characteristics, such as external appearance, personality traits, susceptibility to particular diseases, drug responses, and equilibrium among internal organ functions. According to SCM, herbs that belong to a certain constitution cannot be used in patients with other constitutions; otherwise, this practice may result in no effect or in an adverse effect. Thus, the diagnosis of SC type is the most crucial step in SCM practice. The diagnosis, however, tends to be subjective due to a lack of quantitative standards for SC diagnosis. METHODS: We have attempted to make the diagnosis method as objective as possible by basing it on an analysis of quantitative data from various Oriental medical clinics. Four individual diagnostic models were developed with multinomial logistic regression based on face, body shape, voice, and questionnaire responses. Inspired by SCM practitioners' holistic diagnostic processes, an integrated diagnostic model was then proposed by combining the four individual models. RESULTS: The diagnostic accuracies in the test set, after the four individual models had been integrated into a single model, improved to 64.0% and 55.2% in the male and female patient groups, respectively. Using a cut-off value for the integrated SC score, such as 1.6, the accuracies increased by 14.7% in male patients and by 4.6% in female patients, which showed that a higher integrated SC score corresponded to a higher diagnostic accuracy. CONCLUSIONS: This study represents the first trial of integrating the objectification of SC diagnosis based on quantitative data and SCM practitioners' holistic diagnostic processes. Although the diagnostic accuracy was not great, it is noted that the proposed diagnostic model represents common rules among practitioners who have various points of view. Our results are expected to contribute as a desirable research guide for objective diagnosis in traditional medicine, as well as to contribute to the precise diagnosis of SC types in an objective manner in clinical practice.

Variant alleles of the Wnt antagonist FRZB are determinants of hip shape and modify the relationship between hip shape and osteoarthritis.

OBJECTIVE: To test whether single-nucleotide polymorphisms (SNPs) of the FRZB gene are associated with hip shape, and to determine whether FRZB variant alleles affect the relationship between hip shape and radiographic osteoarthritis (OA) of the hip. METHODS: A nested case-control study of Caucasian women, age ≥65 years, from the Study of Osteoporotic Fractures cohort was performed. Cases (n = 451) were defined as subjects with radiographic evidence of incident hip OA during followup, while controls (n = 601) were subjects in whom no radiographic hip OA was identified at baseline or followup. Statistical shape modeling (SSM) of the digitized hip radiographs was performed to assess the shape of the proximal femur, using 10 independent modes of shape variation generated by principal components analysis. In addition, center-edge angle and acetabular depth were assessed as geometric measurements of acetabular shape. The association of the rs288326 and rs7775 FRZB variant alleles with hip shape was analyzed using linear regression. The effect of these alleles on the relationship between hip shape and radiographic hip OA was analyzed using a logistic regression model with or without inclusion of interaction terms. RESULTS: The rs288326 and rs7775 alleles were associated with the shape of the proximal femur (SSM mode 2). There was a significant interaction between the rs288326 SNP and proximal femur shape (SSM mode 2) in predicting radiographic hip OA (P for interaction = 0.022). Among subjects with the rs288326 variant allele, there was an increased likelihood of radiographic hip OA in association with increasing quartiles of proximal femur shape mode 2 (for the fourth quartile of mode 2, odds ratio 2.5, 95% confidence interval 1.15, 5.25; P for linear trend = 0.02). CONCLUSION: The rs288326 and rs7775 FRZB SNPs are associated with the shape of the proximal femur. The presence of the rs288326 SNP alters the relationship between proximal femur shape and incident radiographic hip OA. These findings suggest that FRZB may serve an important role in determining hip shape and may modify the relationship between hip shape and OA.