Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Blood lead levels increase, but remain in normal range with severe weight reduction.

High bone turnover states are known to raise blood lead levels (BPb). Caloric restriction will increase bone turnover, yet it remains unknown if weight reduction increases BPb due to mobilization of skeletal stores. We measured whole blood Pb levels (²⁰⁶Pb) by inductively coupled plasma mass spectrometry in 73 women (age 24–75 years; BMI 23– 61 kg/m²) before and after 6 months of severe weight loss (S-WL), moderate weight loss (M-WL), or weight maintenance (WM). Baseline BPb levels were relatively low at 0.2–6.0 μg/dl, and directly associated with age (r=0.49, P<0.0001). After severe WL (-37.4±9.3 kg, n=17), BPb increased by 2.1±3.9 μg/dl (P<0.05), resulting in BPb levels of 1.3–12.5 μg/dl. M-WL (-5.6±2.7 kg, n=39) and WM (0.3±1.3 kg, n=17) did not result in an increase in BPb levels (0.5±3.2 and 0.0±0.7 μg/dl, M-WL and WM, respectively). BPb levels increased more with greater WL (r=0.24, P<0.05). Bone turnover markers increased only with severe WL and were directly correlated with WL. At baseline, higher calcium intake was associated with lower BPb (r=-0.273, P<0.02), however, this association was no longer present after 6 months. Severe weight reduction in obese women increases skeletal bone mobilization and BPb, but values remain well below levels defined as Pb overexposure.This research was supported by the NIEHS sponsored UMDNJ Center for Environmental Exposures and Disease, Grant number: NIEHS P30ES005022, in part by NIH-AG12161, and a Busch Biomedical Award to SA Shapses.National Institutes of Health: AG12161, to S.A. ShapsesCharles & Johanna Busch Biomedical Grant, to S.A. ShapsesThe published version of this paper is available at: http://www.nature.com/je