59 research outputs found

    Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.

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    BackgroundNeural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.MethodsReplication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS.ResultsOf the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.ConclusionsWe report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis

    Where Do We Go From Here? The Need for Genetic Referrals in Patients who are Deaf or Hard of Hearing: Findings from a Regional Survey

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    Purpose: The purpose of this study was to assess primary health care providers’ knowledge and use of genetic services for children whose hearing screening indicates they may be deaf/hard of hearing (D/HH) and identify areas in which health care providers can be supported to increase family education and referral of families for genetic consultation. Methodology: A survey was developed on current practices, knowledge, and perceived beliefs regarding genetic education and referrals for deafness. The surveys were distributed to pediatricians, family medicine physicians, nurse practitioners, and physician assistants in DC, DE, MD, NJ, NY, PA, VA, and WV. Results: Among 266 respondents, 80% were uninformed about Early Hearing Detection Intervention (EHDI) 1-3-6 guidelines prior to taking the survey. Approximately 55% were not confident about the genetic causes of deafness, 44% rarely consulted genetics professionals, 41% had not referred families to genetics, and 37% were not confident about the importance of genetic referrals. Conclusions: Integrated, targeted, and user-friendly genetics education strategies in the existing EHDI framework are needed to ensure adequate awareness and delivery of genetics services for D/HH children

    Performance of ICD‐10‐CM diagnosis codes for identifying children with Sickle Cell Anemia

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    ObjectiveTo develop, test, and validate the performance of ICD‐10‐CM claims‐based case definitions for identifying children with sickle cell anemia (SCA).Data SourcesMedicaid administrative claims (2016) for children <18 years with potential SCA (any D57x diagnosis code) and newborn screening records from Michigan and New York State.Study DesignThis study is a secondary data analysis.Data Collection/Extraction MethodsUsing specific SCA‐related (D5700, D5701, and D5702) and nonspecific (D571) diagnosis codes, 23 SCA case definitions were applied to Michigan Medicaid claims (2016) to identify children with SCA. Measures of performance (sensitivity, specificity, area under the ROC curve) were calculated using newborn screening results as the gold standard. A parallel analysis was conducted using New York State Medicaid claims and newborn screening data.Principal FindingsIn Michigan Medicaid, 1597 children had ≥1 D57x claim; 280 (18 percent) were diagnosed with SCA. Measures of performance varied, with sensitivities from 0.02 to 0.97 and specificities from 0.88 to 1.0. The case definition of ≥1 outpatient visit with a SCA‐related or D571 code had the highest area under the ROC curve, with a sensitivity of 95 percent and specificity of 92 percent. The same definition also had the highest performance in New York Medicaid (n = 2454), with a sensitivity of 94 percent and specificity of 86 percent.ConclusionsChildren with SCA can be accurately identified in administrative claims using this straightforward case definition. This methodology can be used to monitor trends and use of health services after transition to ICD‐10‐CM.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154614/1/hesr13257.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154614/2/hesr13257_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154614/3/hesr13257-sup-0001-Authormatrix.pd

    Genetics and Public Health in the 20th Century.

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    Newborn Screening for Krabbe Disease and Other Lysosomal Storage Disorders: Broad Lessons Learned

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    Newborn screening (NBS) for Krabbe disease (KD) began in New York (NY) in August 2006. In summary, after eight years of screening there were five infants identified with early-onset Krabbe disease. Four underwent transplant, two are surviving with moderate to severe handicaps, and two died from transplant-related complications. An additional forty-six asymptomatic infants were found to be at moderate or high risk for disease. Screening for KD is both analytically and medically challenging; since screening for KD possesses both of these challenges, and many more, the lessons learned thus far could be used to predict the challenges that may be faced when screening for other lysosomal storage disorders (LSDs). This paper briefly reviews reports of NBS for LSDs from varied world programs. The challenges encountered in screening for KD in NY will be highlighted, and this experience, combined with hindsight, will inform what may be expected in the future as screening for LSDs expands