Common DNA variants predict tall stature in Europeans.

Genomic prediction of the extreme forms of adult body height or stature is of practical relevance in several areas such as pediatric endocrinology and forensic investigations. Here, we examine 770 extremely tall cases and 9,591 normal height controls in a population-based Dutch European sample to evaluate the capability of known height-associated DNA variants in predicting tall stature. Among the 180 normal height-associated single nucleotide polymorphisms (SNPs) previously reported by the Genetic Investigation of ANthropocentric Traits (GIANT) genome-wide association study on normal stature, in our data 166 (92.2 %) showed directionally consistent effects and 75 (41.7 %) showed nominally significant association with tall stature, indicating that the 180 GIANT SNPs are informative for tall stature in our Dutch sample. A prediction analysis based on the weighted allele sums method demonstrated a substantially improved potential for predicting tall stature (AUC = 0.75; 95 % CI 0.72-0.79) compared to a previous attempt using 54 height-associated SNPs (AUC = 0.65). The achieved accuracy is approaching practical relevance such as in pediatrics and forensics. Furthermore, a reanalysis of all SNPs at the 180 GIANT loci in our data identified novel secondary association signals for extreme tall stature at TGFB2 (P = 1.8 × 10(-13)) and PCSK5 (P = 7.8 × 10(-11)) suggesting the existence of allelic heterogeneity and underlining the importance of fine analysis of already discovered loci. Extrapolating from our results suggests that the genomic prediction of at least the extreme forms of common complex traits in humans including common diseases are likely to be informative if large numbers of trait-associated common DNA variants are available.

Safety and Efficacy of Bilateral Epiphysiodesis Surgery to Reduce Final Height in Extremely Tall Adolescents - A Follow-up Study.

INTRODUCTION: Treatment options in patients with extreme tall stature are limited. Bilateral epiphysiodesis has emerged as a possible treatment method aiming to reduce final height. However, there is still insufficient data on long-term safety and final height outcome. Therefore, the aim of this study was to assess the efficacy and safety of bilateral epiphysiodesis to reduce final adult height in tall adolescents. METHODS: The study population consisted of 72 patients with extreme tall stature who were followed at the Pediatric Endocrine Clinic at the Karolinska University Hospital, Stockholm (Sweden) and subsequently underwent bilateral epiphysiodesis around the knees (girls n=45, boys n=27). RESULTS: When compared to the final height prediction at time of surgery, the procedure significantly reduced the achieved final height by a mean of 3.6 cm ± 0.4 cm in girls (p<0.001; 26.0 ± 2.9 % reduction) and 8.6 ± 0.9 cm in boys (p<0.001; 40.5 ± 3.0 % reduction). Furthermore, a negative correlation was observed between the absolute height reduction and the bone age at time of surgery, which was stronger in boys (r=-0.63, p<0.001) than in girls (r=-0.44, p<0.001). Besides reducing final height, body proportions were affected in all patients subjected to bilateral epihyseodesis. However, as tall individuals typically have relatively long legs, body proportions were rather normalized after the surgery. There were no serious complications reported. CONCLUSION: This study suggests that bilateral epiphysiodesis is an efficient and safe method to reduce final height in extremely tall adolescent girls and boys. The achieved height reduction was higher in boys and when performed at an earlier bone age. Importantly, no serious side-effects were reported. However, a continued follow-up is still warranted to detect any potential rare complications.

Adult height is associated with risk of cancer and mortality in 5.5 million Swedish women and men.

BACKGROUND: Previous studies have indicated that taller individuals are at greater risk of developing cancer. Death from cancer and other specific causes have also been linked to height, but the results have been inconclusive. We aimed to shed further light on the associations between height, cancer incidence and mortality. METHODS: We conducted a nationwide, population-based prospective cohort study, including 5.5 million Swedish women and men (aged 20-74). They were followed over a period of up to 54 years. Heights were retrieved from national registers (mainly the Passport Register where heights are most often self-reported). The risks of overall and specific cancers, as well as overall and cause-specific mortality, were presented as HR with 95% CIs per 10 cm increase in height. RESULTS: A total of 278 299 cases of cancer and 139 393 cases of death were identified. For overall cancer, HR was 1.19 (1.18-1.20) in women and 1.11 (1.10-1.12) in men for every 10 cm increase in height. All 15 specific cancer types were positively associated with height-most strongly for malignant melanoma in both genders, with HRs of 1.39 (1.35-1.43) in women and 1.34 (1.30-1.38) in men. For overall mortality, HR was 0.98 (0.97-0.99) in women and 0.91 (0.90-0.92) in men for every 10 cm increase in height. Cancer mortality was increased in taller individuals, with HR 1.15 (1.13-1.17) in women and 1.05 (1.03-1.07) in men for every 10 cm increase in height, whereas shorter individuals had increased overall mortality due to a number of other causes, such as cardiovascular disease. CONCLUSION: Overall and specific cancer risks, particularly malignant melanoma, were positively associated with height. Cancer mortality also increased with height. In contrast, overall mortality was decreased with height, particularly in men due to inverse associations with height for other causes of death.

The Physiology of Childhood Growth: Hormonal Regulation.

The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.

Risks of malignant and non-malignant tumours in tall women treated with high-dose oestrogen during adolescence.

BACKGROUND/AIM: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. METHODS: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. RESULTS: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or non-malignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-∞) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. CONCLUSION: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort.

Efficacy and Safety of Percutaneous Epiphysiodesis Operation around the Knee to Reduce Adult Height in Extremely Tall Adolescent Girls and Boys.

Objective. The aim was to determine efficacy and safety of a surgical method to reduce adult height in extremely tall adolescents. Methods. Data for all girls (n = 12) and boys (n = 9) in our center subjected to bilateral percutaneous epiphysiodesis around the knee who had reached final height were included. Final height predictions were based on hand and wrist X-rays before surgery. Results. When compared to prediction, adult height was reduced by 4.1 ± 0.7 cm in treated girls (P < .001) and 6.4 ± 0.7 cm in treated boys (P < .001) corresponding to a 33.6 ± 3.4% and 33.6 ± 4.2% reduction of remaining growth, respectively. Besides mild to moderate postoperative pain reported in 9 operated individuals, no other side effects were reported. Postoperative X-rays confirmed growth plate closure and absence of leg angulations. Conclusions. Bilateral epiphysiodesis is an effective and safe method to reduce adult height in extremely tall girls and boys.