The HUNT study: A population-based cohort for genetic research

Brumpton, Ben; Graham, Sarah E.; Surakka, Ida; Skogholt, Anne Heidi; Løset, Mari; Fritsche, Lars G.; Wolford, Brooke N.; Zhou, Wei; Nielsen, Jonas B.; Holmen, Oddgeir L.; Gabrielsen, Maiken Elvestad; Thomas, Laurent F.; Bhatta, Laxmi; Rasheed, Humaira; Zhang, He; Kang, Hyun Min; Hornsby, Whitney E.; Moksnes, Marta R; Coward, Eivind; Melbye, Mads; Giskeødegård, Guro F.; Fenstad, Jørn; Krokstad, Steinar; Næss, Marit; Boehnke, Michael; Abecasis, Gonçalo R.; Åsvold, Bjørn Olav; Hveem, Kristian; Willer, Cristen J.

doi:10.1016/j.xgen.2022.100193

Cited by 44 publications

(40 citation statements)

References 79 publications

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“…Preeclampsia/eclampsia was ascertained by linkage to the Medical Birth Registry of Norway, which defines preeclampsia as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg accompanied by proteinuria >0.3 g/24 h or >1+ on urine dipstick 91 . The current analysis includes genetic data from approximately 90% of participants from HUNT2 (1995-1997) and HUNT3 (2006-2008) who were genotyped by genome-wide SNP arrays in 2015 92,93 . Genotyping, quality control metrics, and imputation have been described previously 92 .…”

Section: Methodsmentioning

confidence: 99%

“…The current analysis includes genetic data from approximately 90% of participants from HUNT2 (1995-1997) and HUNT3 (2006-2008) who were genotyped by genome-wide SNP arrays in 2015 92,93 . Genotyping, quality control metrics, and imputation have been described previously 92 . Briefly, one of three different Illumina HumanCoreExome arrays (HumanCoreExome12 v1.0, HumanCoreExome12 v1.1, and UM HUNT Biobank v1.0) were used for genotyping the HUNT2 and HUNT3 samples 92 .…”

Section: Methodsmentioning

confidence: 99%

“…Genotyping, quality control metrics, and imputation have been described previously 92 . Briefly, one of three different Illumina HumanCoreExome arrays (HumanCoreExome12 v1.0, HumanCoreExome12 v1.1, and UM HUNT Biobank v1.0) were used for genotyping the HUNT2 and HUNT3 samples 92 . Samples and variants with call rate <99% were excluded.…”

Section: Methodsmentioning

confidence: 99%

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Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension

Honigberg

Truong

Khan

et al. 2022

Preprint

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Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and offspring outcomes. Current tools for prediction, prevention, and treatment are limited. In discovery analysis, we tested the association of maternal DNA sequence variants with preeclampsia in 17,150 cases and 451,241 controls and with gestational hypertension in 8,961 cases and 184,925 controls using multi-ancestry meta-analysis. We identified 12 independent loci associated with preeclampsia/eclampsia, 7 of which are novel (including MTHFR-CLCN6, WNT3A, PGR, FLT1, and RGL3), and 7 loci associated with gestational hypertension. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development, and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external datasets, independent of first-trimester risk markers. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and advance pregnancy risk stratification.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension

Honigberg

Truong

Khan

et al. 2022

Preprint

Self Cite

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“…Genotyping was performed using a custom Illumina HumanCoreExome array (UM HUNT Biobank v.2.0) on 18 722 individuals (20). Ancestry was predicted using principal components of ancestry projected onto the 1000 Genomes Project.…”

Section: Methodsmentioning

confidence: 99%

Body Composition, Cardiometabolic Risk Factors and Comorbidities in Psoriasis and the Effect ofHLA-C*06:02Status: The HUNT Study, Norway

Solvin

Bjarkø

Thomas

et al. 2022

Preprint

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Psoriasis has been associated with increased adiposity measures driving systemic inflammation, which may lead to metabolic dysfunction and comorbidities. In this population-based, cross-sectional study, we used data from 56 042 individuals in the fourth wave of the Trøndelag Health Study (HUNT4), to investigate the associations between psoriasis and body composition measures assessed using bioelectrical impedance analysis, cardiometabolic risk factors, and comorbidities. Further, we investigated the associations between HLA-C*06:02 status, a potential clinical biomarker for a distinct psoriasis endotype, and these outcomes. Psoriasis was associated with increased adiposity measures, including increased body and visceral fat, and lower levels of skeletal muscle and soft lean mass, as well as higher prevalences of cardiovascular, respiratory and endocrine disorders. HLA-C*06:02 -positive individuals with psoriasis had lower levels of hsCRP, increased prevalence of atrial fibrillation and decreased prevalence of migraine. Our results point to altered body composition in psoriasis with increased levels of fat, and particularly metabolically active visceral fat, and provide support for a broad clinical approach to psoriatic patients in a general population.

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“…Additional phenotypic information is collected by integrating national registers. Approximately 90% of participants from HUNT2 and HUNT3 were genotyped in 2015 [18], 2202 HUNT individuals had low-pass sequencing performed to improve imputation, and the genotype and phenotype data used in the subsequent analyses are exclusively from the HUNT2 and HUNT3 surveys.…”

Section: Hunt Studymentioning

confidence: 99%

Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study

et al. 2022

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The Barker Hypothesis posits that adverse intrauterine environments result in fetal growth restriction and increased risk of cardiometabolic disease through developmental compensations. Here we introduce a new statistical model using the genomic SEM software that is capable of simultaneously partitioning the genetic covariation between birthweight and cardiometabolic traits into maternally mediated and offspring mediated contributions. We model the covariance between birthweight and later life outcomes, such as blood pressure, non-fasting glucose, blood lipids and body mass index in the Norwegian HUNT study, consisting of 15,261 mother-eldest offspring pairs with genetic and phenotypic data. Application of this model showed some evidence for maternally mediated effects of systolic blood pressure on offspring birthweight, and pleiotropy between birthweight and non-fasting glucose mediated through the offspring genome. This underscores the importance of genetic links between birthweight and cardiometabolic phenotypes and offer alternative explanations to environmentally based hypotheses for the phenotypic correlation between these variables.

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The HUNT study: A population-based cohort for genetic research

Cited by 44 publications

References 79 publications

Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension

Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension

Body Composition, Cardiometabolic Risk Factors and Comorbidities in Psoriasis and the Effect ofHLA-C*06:02Status: The HUNT Study, Norway

Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study

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