WGHS participants had a mean (SD) BMI of25.8 (4.9) kg/[m.sup.2] and mean WC of 88.5(14.1) cm.
In the WGHS overall, each unit increase in BMI (kg/[m.sup.2]) corresponded to a 1.01% increase in TG (P < 0.0001), and each unit increase in WC (cm) corresponded to a 1.00% increase in TG (P < 0.0001).
We examined these assumptions by comparing effects of each SNP in normal vs overweight/obese adiposity strata according to BMI in the WGHS, scaling within stratum effects by the weights used to construct the TG-wGRS (see Fig.
We metaanalyzed the previously reported continuous trait BMI X TG-wGRS (INTER99, HEALTH2006, MDC, and GLACIER) and WC X TG-wGRS (INTER99 and HEALTH 2006) interaction-effect estimates on TG together with BMI (continuous trait) X TG-wGRS and WC (continuous trait) X TG-wGRS estimates from the WGHS. For a total sample of n = 40 026 (more than double the previous sample), in our metaanalysis of BMI X TG-wGRS on TG, we observed a statistically significant consensus interaction ([P.sub.interaction] = 0.001) with significant heterogeneity ([I.sup.2] = 63.2% and P = 0.028) (Fig.
In the current study, we have replicated the interactions between adiposity (BMI and WC) and TG-wGRS based on TG-associated genetic variants in relation to TG in about 22000 US women from the WGHS cohort.
Moreover, our results show that in the large sample of the WGHS, the interaction between GRS adiposity and TG risk was independent of a range of potential confounders, including diet, physical activity, smoking status, and comorbidities.
Chasman, also an assistant professor at Harvard Medical School, added: "Of the loci for timing of menopause, three were already strong but not proven candidates in the NHS; these loci reached genome-wide significance in the WGHS
alone, supplementing the meta-analysis by a second mode of validation through replication.
In this report we describe the WGHS and its parent WHS from the perspectives of cohort assembly, follow-up, endpoint validation, baseline plasma phenotyping, DNA extraction, genotyping, participant confidentiality, power and sample size and discuss the WGHS in context with other ongoing GWAS being performed in related areas.
All members of the WGHS cohort were participants in the WHS who provided an adequate baseline blood sample for plasma and DNA analysis and who gave consent for blood-based analyses and long-term follow-up.
The WGHS cohort described here comprises 28 345 (70.6%) of the 39 876 WHS participants who provided a baseline blood sample adequate for plasma and DNA analysis before randomization and consented to ongoing analyses linking blood-derived observations with baseline risk factor profiles and incident disease events.
All participants in the WGHS provided baseline blood samples collected in EDTA and citrate that were shipped overnight in cooled packaging to a central storage facility where they were separated into plasma and buffy-coat fractions, divided into aliquots, and stored in liquid nitrogen.
DNA samples are genotyped in batches of 95 WGHS participants with 1 CEPH (Centre d'Etude de Polymorphism Humain) DNA (NA10846) included to monitor genotyping consistency and plate orientation.