New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Trends in human birth weight across two successive generations

OBJECTIVE: To determine the correlation between parental and offspring birthweight (BW) in India. METHODS: The study involved two birth cohorts of successive generations. The parental cohort comprised of 472 fathers and 422 mothers from an earlier study. Details of their anthropometry at birth and in adulthood were available. 1525 children born to them comprised the offspring cohort. BW was obtained from hospital records for the offspring cohort. Odds ratios and regression coefficients were calculated to estimate the risks of a low birth weight (LBW) parent producing a LBW baby and quantitate the effects after adjusting for confounders. RESULTS: A LBW mother had a 2.8 times risk (95%CI 1.2-6.4) of delivering a LBW baby (p=0.02) and a LBW father was twice as likely to produce a LBW baby (OR 2.2; 95%CI 1.0 - 4.8; p=0.05). Every 100g increase in maternal BW was associated with an increase in offspring BW of 14 g; the equivalent figure for paternal BW was 18.1g (p&lt; 0.001 for both). Between the generations, the incidence of LBW decreased from 19.7% to 17.2% (p=0.1). Mean BW increased in males (2846 g vs 2861 g; p=0.59) but not in females (2790 g vs 2743 g; p=0.08). CONCLUSION: Both maternal and paternal BW are strong determinants of offspring BW. The effect of mothers' BW on offspring BW is weaker than that seen in developed nations. Stronger intrauterine constraint exhibited by Indian women secondary to a higher prevalence of growth restriction in utero may be responsible. Paternal effects may be governed by paternal genes inherited by the offspring