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- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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2. |
- Eriksson, Elisabeth, 1971-
(author)
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Återkoppling i lågstadieklassrum
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Återkoppling är en del av det vardagliga arbetet i klassrummet och även en del av lärares bedömningspraktik. Syftet med avhandlingen är att utforska och begreppsliggöra den återkoppling som kommuniceras från lärare till elev i det vardagliga arbetet i lågstadieklassrum. Pragmatism, symbolisk interaktionism och barndomssociologi utgör avhandlingens teoretiska perspektiv. Som metod användes konstruktivistisk grundad teori, som präglas av en iterativ process där analys och datainsamling sker i växelverkan. Data samlades in genom observationer i fyra klassrum, intervjuer med 13 lärare, fokusgrupper med 23 elever samt informella samtal. I resultaten presenteras en kategorisering av den återkoppling som lärare ger elever. I en systematisk konceptualisering av lärares rationaler för återkoppling synliggörs de överväganden som påverkar hur lärare ger återkoppling. Eleverna tolkade lärares återkoppling som förmedlande av måsten. Vidare delade lärare och elever en upptagenhet av att konstruera klarhet i återkopplingen, vilket gjordes utifrån tillförlitlighet och förståelse. Tillsammans ger delstudierna en bild av klassrumsåterkoppling som relationellt och komplext. Rättvisa beskrivs som eftersträvansvärt men svårt. Avhandlingen bidrar med beskrivningar av den återkoppling som kommuniceras i interaktionen mellan lärare och elever på lågstadiet, samt begrepp för att diskutera och förstå den.
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3. |
- Ntalla, Ioanna, et al.
(author)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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