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Neonatal screening for detection of deafness.

To assess various methods of early detection of deafness, a longtudinal study of infants born in the Jerusalem area was performed. The 17,731 newborns were tested by an acoustic signal generator hearing test (Apriton), and the "at risk" for deafness register was applied to them. Twenty-five children were identified as deaf, 14 with severe or profound hearing loss and 11 with moderate or moderately severe loss. The screening hearing test did not prove to be sensitive enough for detection of deafness in newborns, and, therefore, is not considered valid for screening purposes. The at risk for deafness register, which in our program covered 20% of the entire newborn population, proved to be to expensive and impractical; a restricted register, including approximately 7% of the newborns, is suggested.

Acoustic Stimulation

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank.

The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF &#x223c;0.001%) in the UK Biobank (UKBB) exome-sequencing data to characterize recessive effects in 175,587 individuals across 311 common diseases. A total of 6.5% of individuals carry putatively damaging CH variants, 90% of which are only identifiable upon phasing rare variants (MAF&#xa0;<&#xa0;0.38%). We identify six recessive gene-trait associations (p&#xa0;<&#xa0;1.68&#xa0;&#xd7;&#xa0;10-7) after accounting for relatedness, polygenicity, nearby common variants, and rare variant burden. Of these, just one is discovered when considering homozygosity alone. Using longitudinal health records, we additionally identify and replicate a novel association between bi-allelic variation in ATP2C2 and an earlier age at onset of chronic obstructive pulmonary disease (COPD) (p&#xa0;<&#xa0;3.58&#xa0;&#xd7;&#xa0;10-8). Genetic phase contributes to disease risk for gene-trait pairs: ATP2C2-COPD (p&#xa0;= 0.000238), FLG-asthma (p&#xa0;= 0.00205), and USH2A-visual impairment (p&#xa0;= 0.0084). We demonstrate the power of phasing large-scale genetic cohorts to discover phenome-wide consequences of compound heterozygosity.

Humans