Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

INTRODUCTORY PARAGRAPHTo identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (N=10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in thirteen replication studies (N=27,591). Rs900400 near LEKR1 and CCNL1 (P=2×10−35), and rs9883204 in ADCY5 (P=7×10−15) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and type 2 diabetes susceptibility,1 providing evidence that the well described association between lower birth weight and subsequent type 2 diabetes2,3 has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, the 9% of Europeans with 4 birth weight-lowering alleles were, on average, 113g (95%CI 89-137g) lighter at birth than the 24% with 0 or 1 allele (Ptrend=7×10−30). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy.4

Embryo freezing does not adversely affect perinatal outcome in terms of prematurity, low birthweight and being small for gestational age versus the fresh embryo transfer and the outcome is similar or even better, particularly regarding fetal growth. Our study, which is one of the largest on FET pregnancies, provides further evidence on the safety of FET.

OBJECTIVE:To study the association between body size from birth to adulthood and self-reported symptoms of polycystic ovary syndrome (PCOS), particularly hirsutism and menstrual disturbances. DESIGN: Longitudinal, population-based study of a cohort of women born in 1966 in northern Finland. The study population included 2007 women who were not pregnant and did not use hormonal contraception. Of these 528 (26%) had self-reported symptoms of PCOS. RESULTS: Weight at birth, gestational age, being small for gestational age or growth retardation at birth were not associated with PCOS symptoms at 31 y. An increased risk of PCOS symptoms was observed among women with abdominal obesity (waist/ hip ratio 485th percentile) at 31 y who had normal weight in adolescence and were overweight (body mass index (BMI) 25.0-29.9 kg/m 2 ) or obese (BMI430.0 kg/m 2 ) at 31 y (relative risk (RR) (95% CI) 1.44(1.10-1.89)), and among women with abdominal obesity who were overweight or obese at both 14 and 31 y (1.71 (1.30-2.24)). A total of 30% and 41% of the women with PCOS symptoms in these groups could be attributed, respectively, to overweight, obesity and abdominal obesity at 31 y. CONCLUSIONS: These results suggest that obesity in adolescence and in adulthood, and also weight gain after adolescence, particularly in the presence of abdominal obesity, are associated with self-reported PCOS symptoms in adulthood. Thus, based on the results from intervention studies treating PCOS and the results of this study, the prevention of obesity and abdominal obesity is important among young women.