We compared our significant loci to all eQTL Catalogue RNA-Seq datasets containing QTLs for gene expression, exon expression, transcript usage and txrevise event usage; eQTL Catalogue microarray datasets containing QTLs for gene expression; and GTEx v7 datasets containing QTLs for gene expression (Kerimov et al., 2021). In a recent preprint work, Ward et al. ), Finska Lkaresllskapet (H.L.) The enrichment of the alleles likely allowed us to detect the associations with PCOS in the Finnish and Estonian populations, whereas in populations with lower minor allele frequencies, much larger study populations would need to be used. In this analysis, the FinnGen lead variant rs145598156 remained genome-wide significant (P = 4.5108, OR = 13.5 [5.3534.38]) (Table I and Supplementary Fig. Additionally, we replicated the previously reported associations for Erb-B2 receptor tyrosine kinase 4 (ERBB4), DENN domain containing 1A (DENND1A), FSH subunit beta (FSHB) and zinc finger and BTB domain containing 16 (ZBTB16). For the purpose of organizing a consolidated irrigation district a petition signed by fifty or a majority of the holders of title to, or evidence of title to land susceptible of irrigation within the proposed district shall be presented to the board of county commissioners of the county in which the lands or the greater portion thereof are situated, which petition shall set forth and . The population-specific imputation reference of 2297 whole-genome sequencing samples was used (Mitt et al., 2017). Fredonia Consolidated Irrigation and Mfg. All authors participated in manuscript editing and review and approved the final version. de Ziegler D, Pirtea P, Fanchin R, Ayoubi JM. In both cases, the lead single nucleotide polymorphisms had tightly linked variants, a frameshift (c.1100delC) and a missense (I157T), in the CHEK2 gene. S2). Jaakko S Tyrmi and Riikka K Arffman contributed equally to this work. When alleles enriched in such populations are causal or linked to causal variation, increased statistical power is present, enabling their detection in an association analysis (Lim et al., 2014; Prohaska et al., 2019). The funders had no role in study design, data collection and analysis, publishing or preparation of the manuscript. The meetings will be held on: Please complete our Prop 218 Support Form to add your name to our list of Supporters: Consolidation Irrigation District Copyright 2023 - All Rights Reserved. Although a metabolic link between MYO10 and PCOS seems likely, further research is needed to characterize the role of MYO10 in PCOS. Since considering most significant variants as the causal ones would lead to an underestimation of the total variance explained at each locus, we next performed conditional analyses, which were carried out similarly to the main association testing using SAIGE (Zhou et al., 2018). 19 ), 297338 (J.K.), 307247 (J.K.), 344695 (H.L. Lim SS, Kakoly NS, Tan JWJ, Fitzgerald G, Bahri Khomami M, Joham AE, Cooray SD, Misso ML, Norman RJ, Harrison CL et al. Association analysis was carried out using SAIGE (v0.38) software to implement a mixed logistic regression model with a year of birth and 10 PCs as covariates in step I. @
Summary of association results of the genome-wide association meta-analysis of polycystic ovary syndrome. Johannes Kettunen, 19, Board of Directors Meeting In addition to the reproductive features, PCOS is also characterized by metabolic disturbances such as obesity, insulin resistance and dyslipidemia (Ollila et al., 2016; Lim et al., 2019; Barber and Franks, 2021). Residential customers do not receive a monthly water bill. For validation, we used an independent dataset from the Estonian Biobank, including 2812 cases and 89230 controls. Prohaska A, Racimo F, Schork AJ, Sikora M, Stern AJ, Ilardo M, Allentoft ME, Folkersen L, Buil A, Moreno-Mayar JV et al. Recruitment procedures followed the biobank protocols approved by Fimea. Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. Hassayampa Water Coop 26. and Jane and Aatos Erkko Foundation (H.L.). Leveraging polygenic functional enrichment to improve GWAS power. Assistant General Manager Fresno Irrigation District 2907 S. Maple Avenue Fresno, CA 93725 . In colocalization analyses, all posterior probabilities for a shared causal variant were lower than 0.8. Considering the complex nature of the syndrome, it is likely that both genetic and environmental factors contribute to its development (Abbott et al., 2019; Koivuaho et al., 2019; Moghetti and Tosi, 2021). Despite the high prevalence of the syndrome, the origins of PCOS remain unknown. The age- and BMI-adjusted GWAS meta-analysis summary statistics are available for download from the GWAS Catalog with accession numbers GCST90044902 and GCST90044903. Over 8,000 cubic feet at $1.25/1,000 cubic feet. Leitsalu L, Haller T, Esko T, Tammesoo ML, Alavere H, Snieder H, Perola M, Ng PC, Mgi R, Milani L et al. Low-penetrance susceptibility to breast cancer due to. %PDF-1.5
S1). Under state law, divisions of special districts should: The Board of Directors worked with census data and outside consultants to assess Consolidated Irrigation Districts population and communities of related interests to develop preliminary options for the five divisions of Consolidated Irrigation District by February 2022. Center for Life Course Health Research, Faculty of Medicine, Aapistie 5A, PO Box 5000, 90014 University of Oulu, Oulu, Finland. Over 117,612 cubic feet/acre at $1.25/1,000 cubic feet. 19, located in Greenacres in the Spokane Valley, began operations in 1966. Bill Stretch Manager Fresno Irrigation District 2907 S. Maple Avenue Fresno, CA 93725 . Testing is due annually, and failure to provide acceptable test results by the due date may result in fines. Genome-wide significant variants in FinnGen data are denoted with purple circles; Estonian Biobank-specific variants are not circled. We conclude that our results based on ICD codes alone are robust, as the effects are in the same direction and do not present significant heterogeneity (phet = 1) compared to those using non-NIH Rotterdam criteria (Supplementary Fig. Kichaev G, Bhatia G, Loh P, Gazal S, Burch K, Freund MK, Schoech A, Pasaniuc B, Price AL. 10 0 obj
Irrigation District 1. Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland. Section 3 Objectives of the District [A] Consolidated Irrigation District No. CHEK2 is a mediator of DNA damage signalling in response to double-stranded DNA breaks. Furthermore, as several studies suggest a causal role for obesity in PCOS (Legro, 2012; Brower et al., 2019; Zhao et al., 2020), we examined the influence of BMI on the detected associations with PCOS. The international evidence-based guideline recommends using the Rotterdam criteria for PCOS diagnosis, requiring the presence of at least two of the following symptoms: oligo- or anovulation, clinical or biochemical hyperandrogenism, or polycystic ovaries seen in ultrasound, after exclusion of related disorders (Teede et al., 2018). endobj
Moreover, we observed consistency in the direction of effects between the three datasets analyzed (discovery, validation and joint meta-analysis) (Fig. This provides consumers with financial recourse in case they perform defective work or violate license regulations. Failure to provide acceptable test results by the due date may result in fines. Sprinkler systems are required to have a backflow prevention device. Lim ET, Wrtz P, Havulinna AS, Palta P, Tukiainen T, Rehnstrm K, Esko T, Mgi R, Inouye M, Lappalainen T et al. We proceeded to test associations using a stepwise analysis, where markers were added to the model until no independent signals were identified. _Z}>>J?jZ||ti]ReSr\On|W/T2CL|04KtQ*o||qZfcu,G_bu#
6(D^aYy>T']@PBFE4 The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa (HUS) approved the FinnGen study protocol (Nr HUS/990/2017). A meta-analysis was performed for the FinnGen and EstBB GWAS incorporating a total of 3609 women with PCOS and 229788 controls. Individuals with PCOS were identified using the ICD-10 code E28.2, and all of the female biobank participants without this diagnosis served as controls. 2069, Consolidated Irrigation District, Corcoran Irrigation District, Empire West Side Irrigation District, Fresno Irrigation District, James Irrigation District, Kings County Water District, Kings River Water District, Laguna Irrigation District, Lakeside . 2019 CCR Water Quality Report We then performed a second meta-analysis including the two GWAS adjusted for BMI from both cohorts. The Market Court imposed a total penalty payment of EUR 50.000 on HUS regarding the direct procurement of waste disposal bags and tissue paper products.14 The next two decisions on the direct We also tested if conditioning the discovery GWAS results with I157T and validation GWAS with c.1100delC would affect the significance of the lead variants. The Consolidated Irrigation District (CID or District) is seeking approval from landowners to increase its assessments on land in the District. With this definition, there were 797 cases and 140558 controls. To find your division on the new map, click on the image below which will take you to our Find your Division tool. 9Y#SVQ
u[?S0i(qn/(sH-Rh JypSh"E(=&JPFq@0pV5zu+ }y8~.Fx[hS.]_uoj!xvfn? Pre-phasing was conducted using Eagle v2.3 software (Loh et al., 2016) (number of conditioning haplotypes Eagle2 uses when phasing each sample was set to: Kpbwt = 20000), and imputation was carried out using Beagle 4.1 with effective population size ne = 20000. Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression. 13 were here. Regional plot for the Estonian Biobank lead variant in the same locus 22q11 before and after conditional analysis with linked missense variant (rs17879961) are shown in (C) and (D). Summer Commercial Excess Rates Mustofa MK, Tanoue Y, Tateishi C, Vaziri C, Tateishi S. Roles of Chk2/CHEK2 in guarding against environmentally induced DNA damage and replication-stress. <>
Samples with ambiguous gender, those with high genotype missingness >5% and outliers in the population structure (>4 SD from the mean on the first two dimensions of principal component (PC) analysis) were omitted. The value of studying genetic isolates, such as the Finnish population, has been accepted for decades (Martin et al., 2018). Adaman Irrigation Water Delivery District #36 4. Ruth KS, Day FR, Hussain J, Martnez-Marchal A, Aiken CE, Azad A, Thompson DJ, Knoblochova L, Abe H, Tarry-Adkins J et al. ), Finska Lkaresllskapet (H.L.) 2022 Consolidated Irrigation District No. This work has received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement No. The average effect sizes of the novel alleles described in chromosome 22 (OR = 1.693.01) (Table I) were higher than the effects observed for alleles associated with PCOS in the rest of the common variants described (OR = 1.061.40), which could be explained by the often-observed inverse relationship between allele frequency and effect size (Manolio et al., 2009). We lifted the GWAS summary statistics over to the hg38 build to match the eQTL catalogue and convert the summary statistics to variant call format. Body mass index and polycystic ovary syndrome: a 2-sample bidirectional Mendelian randomization study. 2021 CCR Water Quality Report Consolidated Irrigation District No. 2nd Wednesday of the month Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland. Suite C A final plan was submitted to the Board of Directors for a vote of approval at their meeting on March 9, 2022. Functional characterization of this locus revealed a frameshift variant, c.1100delC (rs555607708, P = 1.68109, OR = 13.46 [5.6831.89]) in CHEK2, with a high LD (r2 = 0.95) with the lead variant. General Notes for Water System Construction Main Line Detail Flush Point Detail We identified three novel genome-wide significant associations with PCOS, with two putative independent causal variants in the checkpoint kinase 2 (CHEK2) gene and a third in myosin X (MYO10). ), 321763 (T.P. Two out of the three novel genome-wide significant variants associating with PCOS, rs145598156 (P = 3.6108, odds ratio (OR) = 3.01 [2.024.50] minor allele frequency (MAF) = 0.005) and rs182075939 (P = 1.91016, OR = 1.69 [1.491.91], MAF = 0.04), were found to be enriched in the Finnish and Estonian populations and are tightly linked to a deletion c.1100delC (r2 = 0.95) and a missense I157T (r2 = 0.83) in CHEK2. We thank all FinnGen and EstBB participants for offering us the valuable resources. 14 from January 1, 2014 through December 31, 2016. CID plays an active role in managing our groundwater basin; overseeing pumping, recharge and monitoring. Financial recourse when hiring Consolidated Irrigation District 19. Lee H, Oh JY, Sung YA, Chung H, Kim HL, Kim GS, Cho YS, Kim JT. 813707 (N.P.-G., T.L. Finnish Institute for Health and Welfare, Helsinki, Finland. Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. CHEK2 can be considered an important factor in the quality control of cells. Genetic insights into the biological mechanisms governing human ovarian ageing. Department of Clinical Genetics, Faculty of Medicine and Health Technology, Tampere University Hospital and Tampere University, Tampere, Finland. An interaction between BMI and PCOS-associated variants has previously been suggested (Wojciechowski et al., 2012), and interestingly, the c.1100delC variant in CHEK2 has recently been shown to predispose particularly obese carriers to the development of breast cancer (Greville-Heygate et al., 2020). The backflow testing process checks your plumbing to ensure dirty water does not infiltrate the drinking water supply. Formatting and preparation of the FinnGen association data for downstream analysis were managed with workflow management software STAPLER (Tyrmi, 2018). Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in northern Europe. 120 N Greenacres Road Spokane Valley WA 99016 (509) 924-3656 Office hours: 8:00 am to 5:00 pm. x[oF?F]@Q`ri1E(3pigKpZt8k-"5=N}[o[s=tK{i}]w~Pglu|tQnJ;>2*%N May Board Meeting will be Thursday, May 11th at 7:00 pm Two out of the three novel genome-wide significant variants associating with PCOS, rs145598156 (P = 3.610 8, odds ratio (OR) = 3.01 [2.02-4.50] minor allele frequency (MAF) = 0.005) and rs182075939 (P = 1.910 16, OR = 1.69 [1.49-1.91], MAF = 0.04), were found to be enriched in the Finnish and Estonian populations and are tightly linked to a . In this study, we found two independent novel associations for PCOS on 22q11.2. The Consolidated Irrigation District ("CID") made a Public Records Act request for certain public records in City's possession regarding the CEQA proceedings. Finnish Institute for Health and Welfare, Helsinki, Finland. Nelis M, Esko T, Mgi R, Zimprich F, Zimprich A, Toncheva D, Karachanak S, Piskkov T, Balak I, Peltonen L et al. The map met all redistricting criteria and made the least number of changes to the 2010 approved map. CID is responsible for local, state and federal regulatory compliance and reporting. The .gov means its official. Our goal is to ensure our growers have access to reliable, high quality, surface and groundwater for the foreseeable future.. FOIA Falck J, Lukas C, Protopopova M, Lukas J, Selivanova G, Bartek J. Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway. V.K. Similarly, I157T, the likely association-driving variant in the EstBB, has a substantially higher allele frequency in the Estonian (0.048) and Finnish (0.029) populations, compared to the non-Finnish, Northwestern European population (0.0025), according to the gnomAD database (Karczewski et al., 2020). Blank form to provide to your certified tester , Email a photo of the completed Backflow Report to. Ward LD, Parker MM, Deaton AM, Tu H, Flynn-Carroll A, Hinkle G, Nioi P. Rare coding variants in five DNA damage repair genes associate with timing of natural menopause. ), Novo Nordisk Foundation grant NNF17OC0026062 (J.K.), the Sigrid Juselius Foundation project grants (T.L., J.K., T.P. Public hearings were advertised through email updates, notices posted in the Selma Enterprise, and this website. Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfldi J, Wang Q, Collins RL, Laricchia KM, Ganna A, Birnbaum DP et al. 200 Coop 3. The MYO10 gene codes for an atypical myosin, which is involved in filopodia formation, phagocytosis and cargo transport in cells (Sousa and Cheney, 2005). 1A). We then conducted a three-stage casecontrol GWAS: in the discovery phase, we had a total of 797 cases and 140558 controls from the FinnGen study. Thus, we did not find enough evidence that two association signals in the genome-wide association analysis and gene expression are consistent with a shared causal variant. Tambets K, Yunusbayev B, Hudjashov G, Ilume A, Rootsi S, Honkola T, Vesakoski O, Atkinson Q, Skoglund P, Kushniarevich A et al. Risal S, Pei Y, Lu H, Manti M, Fornes R, Pui HP, Zhao Z, Massart J, Ohlsson C, Lindgren E et al. Benner C, Havulinna AS, Jrvelin MR, Salomaa V, Ripatti S, Pirinen M. Prospects of fine-mapping trait-associated genomic regions by using summary statistics from genome-wide association studies. In conclusion, we identified two rare population-enriched variants located in CHEK2 that are significantly associated with PCOS. endstream
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The EstBB lead variant rs182075939 presents a higher allele frequency in Estonians (AF = 0.048) compared to Finns (AF = 0.029) and other European populations (AF = 0.0025) according to gnomAD (Karczewski et al., 2020). Gottschau M, Kjaer SK, Jensen A, Munk C, Mellemkjaer L. Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study. Serum anti-Mullerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Notably, the heritability of PCOS is estimated to be around 70% (Vink et al., 2006; Risal et al., 2019). Read more. In this study, we first utilized genome-wide association analyses and data from the FinnGen project and the Estonian Biobank (EstBB) to detect novel PCOS-associated variants in these population isolates. 2020 CCR Water Quality Report endobj
Two of the replicated (FSHB, ZBTB16) and two of the novel associations (MYO10 and CHEK2) did not reach genome-wide significance after adjustment. Home; Your Account. The funders had no role in study design, data collection and analysis, publishing or preparation of the manuscript. Consolidated Irrigation District No. This analysis included 2619 cases and 160321 controls, and a total of 24461102 genetic markers were analyzed. ), the Academy of Finland grants 315921 (T.P. CIDs infrastructure dates back to the late 1800s and therefore requires investment in repairing and replacing these vital resources. Martin AR, Karczewski KJ, Kerminen S, Kurki MI, Sarin A, Artomov M, Eriksson JG, Esko T, Genovese G, Havulinna AS et al. Cohort profile: Estonian Biobank of the Estonian Genome Center, University of Tartu.