Genetics of hip dysplasia - a systematic literature review.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all newborns. DDH increases the risk of osteoarthritis and is the cause of 30% of all total hip arthroplasties in adults < 40 years of age. We aim to explore the genetic background of DDH in order to improve diagnosis and personalize treatment. METHODS: We conducted a structured literature review using PRISMA guidelines searching the Medline, Embase and Cochrane databases. We included 31 case control studies examining single nucleotide polymorphisms (SNPs) in non-syndromic DDH. RESULTS: A total of 73 papers were included for full text review, of which 31 were single nucleotide polymorphism (SNP) case/control association studies. The literature review revealed that the majority of published papers on the genetics of DDH were mostly underpowered for detection of any significant association. One large genome wide association study has been published (N = 9,915), establishing GDF5 as a plausible risk factor. CONCLUSIONS: DDH is known to be congenital and heritable, with family occurrence of DDH already included as a risk factor in most screening programs. Despite this, high quality genetic research is scarce and no genetic risk factors have been soundly established, prompting the need for more research.

COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study.

Objective: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30 â€‹% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome. Design: We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01, R2≥ 0.8 and Hardy-Weinberg equilibrium (HWE) P-value ≥ 0.0001. Significance level was set at p â€‹< â€‹5 â€‹× â€‹10-8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee. Results: Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 (ߠ​= â€‹-0.43, SE â€‹= â€‹0.07, p â€‹= â€‹8.4 â€‹× â€‹10-9) and rs6577334 (ߠ​= â€‹-0.43, SE â€‹= â€‹0.08, p â€‹= â€‹8.9 â€‹× â€‹10-9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis. Conclusions: This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed.

Norwegian children and adolescents in blended families are at risk of larger one-year BMI increments.

AIM: To study how sociodemographic factors and family structure associate with baseline BMI z-scores (BMIz) and BMIz change in 767 Norwegian children aged 6-15 years. METHODS: Baseline BMIz and 1-year BMIz increments in children from the Bergen Growth Study were analysed with linear and logistic regression, according to sociodemographic factors and family structure. A blended family was defined as including a step-parent and/or half-sibling. RESULTS: In a fully adjusted regression model, baseline BMIz were only significantly associated with maternal BMI (b = 0.087, 95%CI 0.067, 0.107). Body Mass Index z-scores increments were larger in children living in a blended family (b = 0.060, 95%CI 0.006, 0.115), with a lower parental education (b = 0.127, 95%CI 0.029, 0.226) and with a higher maternal BMI (b = 0.008, 95%CI 0.001, 0.014). The odds for a large BMIz increment (>1 SD) were higher in children living in blended families (OR 1.82, 95%CI 1.16, 2.88) and with higher maternal BMI (OR 1.07, 95%CI 1.01, 1.13) and lower in 9-11-year-old children (OR 0.44, 95%CI 0.26, 0.77) compared with 12-15-year-olds. CONCLUSION: Body Mass Index z-scores increments were more strongly associated with sociodemographic factors and living in a blended family than baseline BMIz values. BMI z-scores increments could be useful for identifying children at risk of becoming overweight or obese.

Associations between different weight-related anthropometric traits and lifestyle factors in Norwegian children and adolescents: A case for measuring skinfolds.

OBJECTIVES: The purpose of this study was to investigate the association between weight-related anthropometric measures and children's eating habits, physical activity and sedentary lifestyle at a population level. METHODS: Data from the Bergen Growth Study were used to study the association of z-scores of waist circumference (WC), weight-to-height ratio (WHtR), subscapularis (SSF) and triceps (TSF) skinfolds and BMI, with lifestyle factors in 3063 Norwegian children (1543 boys) aged 4-15 years, using linear regression analysis. Each sex was analyzed separately. RESULTS: In a fully adjusted model with additional correction for BMI z-scores, the consumption of vegetables was associated with higher WC (b = 0.03) and TSF (b = 0.05) z-scores in girls. Sedentary behavior was not associated with any of the anthropometric measures. Physical activity was negatively associated with SSF (b = -0.07) and TSF (b = -0.07) z-scores in boys, while a significant negative association was observed with WC (b = -0.02), WHtR (b = -0.03), SSF (b = -0.04) and TSF (b = -0.06) in girls. CONCLUSION: Physical activity was negatively associated with skinfolds in both sexes. The BMI was not related to the level of physical activity, and should be complemented with direct measures of fat tissue, like skinfolds, when studying the effect of physical activity on body composition in children.

Should children with overweight or obesity be excluded from height references?

BACKGROUND AND OBJECTIVES: Growth reference charts are usually based on measurements of children free from a medical condition that affects growth. However, samples collected during the past decades often contain a large proportion of overweight or obese children. Because obesity increases linear growth, the question arises to what extent the percentiles curves for length/height are affected by the presence of children with overweight or obesity. METHODS: Data from two cross-sectional samples of 2-year-old to 18-year-old children were analysed: 12,252 Belgian children, measured in 2002-2004, and 6159 Norwegian children, measured in 2003-2006. The LMS method was used to estimate height-for-age curves with and without children considered overweight or obese according to the International Obesity Task Force thresholds. RESULTS: The prevalence of overweight (including obesity) and obesity was 13.0% and 2.8% in the Belgian and 13.8% and 2.3% in the Norwegian sample. Children were taller when overweight (+0.49 and 0.43 SD, in the Belgian and Norwegian sample, respectively) or obese (+0.73 and 0.72 SD in the Belgian and Norwegian sample, respectively). Effect sizes were smaller in younger and older children, which points to an advanced age of maturation as a possible cause. Excluding overweight and obese children had only a minor impact on the growth curves with largest difference in mean height SD scores -0.09 in the Belgian and -0.12 in the Norwegian sample with a corresponding increase of up to 0.5% and 1.2% in number of children >+2 SD. CONCLUSIONS: Current Belgian and Norwegian growth references for length/height were found to be largely unaffected by the current proportion of overweight and obese children. There is, therefore, no need for revised height charts that exclude overweight or obese children.

TV viewing and obesity among Norwegian children: the importance of parental education.

AIM: To analyse the effect of lifestyle factors on the prevalence of overweight and obesity in 6-15-year-old Norwegian children. METHODS: Questionnaire data on lifestyle factors (sedentary behaviour, activity and eating habits) and prevalence numbers of overweight and obesity based on measured height and weight were analysed using multinomial logistic regression in a sample of 2281 children included in the Bergen Growth Study. RESULTS: More screen time increased the risk of overweight (odds ratio (OR): 1.25; p = 0.02) and obesity (OR: 1.12; p = 0.02) as did the presence of a TV in the child's bedroom (OR: 1.26 (overweight), OR: 1.81 (obese); p = 0.04). The obese children reported less sugar intake than the not overweight children (OR: 0.58; p = 0.01). Higher parental education was associated with less screen time (p = 0.02), lower frequency of TV in the child's bedroom (p = 0.001), more sports (p = 0.005), as well as eating more fruit and vegetables, less sweets, soft drinks and fast food, and more regular meals (for all, p < 0.03). CONCLUSION: Indicators of sedentary lifestyle, such as screen time and the presence of a TV in the child's bedroom, were associated with overweight and obesity in Norwegian schoolchildren. Higher parental education was generally associated with less obesogenic lifestyle.