Limits...
The Norwegian preeclampsia family cohort study: a new resource for investigating genetic aspects and heritability of preeclampsia and related phenotypes.

Roten LT, Thomsen LC, Gundersen AS, Fenstad MH, Odland ML, Strand KM, Solberg P, Tappert C, Araya E, Bærheim G, Lyslo I, Tollaksen K, Bjørge L, Austgulen R - BMC Pregnancy Childbirth (2015)

Bottom Line: Descriptive analyses showed that about 60% of the index women's pregnancies with birth data registered were preeclamptic according to modern diagnosis criteria.We also found that about 41% of the index women experienced more than one preeclamptic pregnancy.In addition, the descriptive analyses confirmed that preeclamptic pregnancies are more often accompanied with delivery complications.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Children's and Women's Health, the Norwegian University of Science and Technology (NTNU), 7491, Trondheim, Norway. linda.tommerdal@ntnu.no.

ABSTRACT

Background: Preeclampsia is a major pregnancy complication without curative treatment available. A Norwegian Preeclampsia Family Cohort was established to provide a new resource for genetic and molecular studies aiming to improve the understanding of the complex pathophysiology of preeclampsia.

Methods: Participants were recruited from five Norwegian hospitals after diagnoses of preeclampsia registered in the Medical birth registry of Norway were verified according to the study's inclusion criteria. Detailed obstetric information and information on personal and family disease history focusing on cardiovascular health was collected. At attendance anthropometric measurements were registered and blood samples were drawn. The software package SPSS 19.0 for Windows was used to compute descriptive statistics such as mean and SD. P-values were computed based on t-test statistics for normally distributed variables. Nonparametrical methods (chi square) were used for categorical variables.

Results: A cohort consisting of 496 participants (355 females and 141 males) representing 137 families with increased occurrence of preeclampsia has been established, and blood samples are available for 477 participants. Descriptive analyses showed that about 60% of the index women's pregnancies with birth data registered were preeclamptic according to modern diagnosis criteria. We also found that about 41% of the index women experienced more than one preeclamptic pregnancy. In addition, the descriptive analyses confirmed that preeclamptic pregnancies are more often accompanied with delivery complications.

Conclusion: The data and biological samples collected in this Norwegian Preeclampsia Family Cohort will provide an important basis for future research. Identification of preeclampsia susceptibility genes and new biomarkers may contribute to more efficient strategies to identify mothers "at risk" and contribute to development of novel preventative therapies.

No MeSH data available.


Related in: MedlinePlus

Primary research strategies for identification of genetic variants across the allele frequency spectrum (adopted from [27]). Genome-wide linkage studies are well suited to identification of genetic variants with allele frequencies below 0.3 % with large effect sizes (OR > 5). Targeted resequencing often leads to identification of genetic variants with allele frequencies between 0.3 and 5 % with moderate effect sizes (2 < OR < 5), but may also be used to identify rare variants with large effects and common variants with modest effects. Traditional GWAS is suited to identification of common genetic variants with modest effect sizes (OR < 2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4666119&req=5

Fig3: Primary research strategies for identification of genetic variants across the allele frequency spectrum (adopted from [27]). Genome-wide linkage studies are well suited to identification of genetic variants with allele frequencies below 0.3 % with large effect sizes (OR > 5). Targeted resequencing often leads to identification of genetic variants with allele frequencies between 0.3 and 5 % with moderate effect sizes (2 < OR < 5), but may also be used to identify rare variants with large effects and common variants with modest effects. Traditional GWAS is suited to identification of common genetic variants with modest effect sizes (OR < 2)

Mentions: In general, the power to detect the effect of genes depends on the effect size, the allele frequency and the sample size. The ability to detect the genes (genetic susceptibility variants) increases when sample size and effect size increase. However, the choice of study design and research strategy is still crucial for the chances of a successful outcome in a genetic study. Figure 2 (adopted from [25, 26]) shows the relationship between effect size and allele frequency. Figure 3 (adopted from [27]) shows what genetic variants that may be detected with three primary strategies (genome-wide linkage, targeted sequencing and genome-wide association). Genome-wide linkage analyses can only be performed in cohorts/collections of biologically related individuals and are preferred when searching for rare variants (allele frequency <0.3 %) expected to have large effect size (odds ratio (OR) > 5). Whereas, genome-wide association studies (GWAS) in case-control or cohort studies, are better suited to identify common variants (allele frequency >5 %) of modest effect size (OR < 2).Fig. 2


The Norwegian preeclampsia family cohort study: a new resource for investigating genetic aspects and heritability of preeclampsia and related phenotypes.

Roten LT, Thomsen LC, Gundersen AS, Fenstad MH, Odland ML, Strand KM, Solberg P, Tappert C, Araya E, Bærheim G, Lyslo I, Tollaksen K, Bjørge L, Austgulen R - BMC Pregnancy Childbirth (2015)

Primary research strategies for identification of genetic variants across the allele frequency spectrum (adopted from [27]). Genome-wide linkage studies are well suited to identification of genetic variants with allele frequencies below 0.3 % with large effect sizes (OR > 5). Targeted resequencing often leads to identification of genetic variants with allele frequencies between 0.3 and 5 % with moderate effect sizes (2 < OR < 5), but may also be used to identify rare variants with large effects and common variants with modest effects. Traditional GWAS is suited to identification of common genetic variants with modest effect sizes (OR < 2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666119&req=5

Fig3: Primary research strategies for identification of genetic variants across the allele frequency spectrum (adopted from [27]). Genome-wide linkage studies are well suited to identification of genetic variants with allele frequencies below 0.3 % with large effect sizes (OR > 5). Targeted resequencing often leads to identification of genetic variants with allele frequencies between 0.3 and 5 % with moderate effect sizes (2 < OR < 5), but may also be used to identify rare variants with large effects and common variants with modest effects. Traditional GWAS is suited to identification of common genetic variants with modest effect sizes (OR < 2)
Mentions: In general, the power to detect the effect of genes depends on the effect size, the allele frequency and the sample size. The ability to detect the genes (genetic susceptibility variants) increases when sample size and effect size increase. However, the choice of study design and research strategy is still crucial for the chances of a successful outcome in a genetic study. Figure 2 (adopted from [25, 26]) shows the relationship between effect size and allele frequency. Figure 3 (adopted from [27]) shows what genetic variants that may be detected with three primary strategies (genome-wide linkage, targeted sequencing and genome-wide association). Genome-wide linkage analyses can only be performed in cohorts/collections of biologically related individuals and are preferred when searching for rare variants (allele frequency <0.3 %) expected to have large effect size (odds ratio (OR) > 5). Whereas, genome-wide association studies (GWAS) in case-control or cohort studies, are better suited to identify common variants (allele frequency >5 %) of modest effect size (OR < 2).Fig. 2

Bottom Line: Descriptive analyses showed that about 60% of the index women's pregnancies with birth data registered were preeclamptic according to modern diagnosis criteria.We also found that about 41% of the index women experienced more than one preeclamptic pregnancy.In addition, the descriptive analyses confirmed that preeclamptic pregnancies are more often accompanied with delivery complications.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Children's and Women's Health, the Norwegian University of Science and Technology (NTNU), 7491, Trondheim, Norway. linda.tommerdal@ntnu.no.

ABSTRACT

Background: Preeclampsia is a major pregnancy complication without curative treatment available. A Norwegian Preeclampsia Family Cohort was established to provide a new resource for genetic and molecular studies aiming to improve the understanding of the complex pathophysiology of preeclampsia.

Methods: Participants were recruited from five Norwegian hospitals after diagnoses of preeclampsia registered in the Medical birth registry of Norway were verified according to the study's inclusion criteria. Detailed obstetric information and information on personal and family disease history focusing on cardiovascular health was collected. At attendance anthropometric measurements were registered and blood samples were drawn. The software package SPSS 19.0 for Windows was used to compute descriptive statistics such as mean and SD. P-values were computed based on t-test statistics for normally distributed variables. Nonparametrical methods (chi square) were used for categorical variables.

Results: A cohort consisting of 496 participants (355 females and 141 males) representing 137 families with increased occurrence of preeclampsia has been established, and blood samples are available for 477 participants. Descriptive analyses showed that about 60% of the index women's pregnancies with birth data registered were preeclamptic according to modern diagnosis criteria. We also found that about 41% of the index women experienced more than one preeclamptic pregnancy. In addition, the descriptive analyses confirmed that preeclamptic pregnancies are more often accompanied with delivery complications.

Conclusion: The data and biological samples collected in this Norwegian Preeclampsia Family Cohort will provide an important basis for future research. Identification of preeclampsia susceptibility genes and new biomarkers may contribute to more efficient strategies to identify mothers "at risk" and contribute to development of novel preventative therapies.

No MeSH data available.


Related in: MedlinePlus