| 1. |
- Kanoni, Stavroula, et al.
(author)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 2. |
- Bentham, James, et al.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 3. |
- Bentham, James, et al.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 4. |
|
|
| 5. |
- Frazier-Wood, Alexis C., et al.
(author)
-
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
-
In: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
-
Journal article (peer-reviewed)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
|
|
| 6. |
- Gaillard, Marie-José, 1953-, et al.
(author)
-
Holocene land-cover reconstructions for studies on land cover-climate feedbacks
- 2010
-
In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 6, s. 483-499
-
Journal article (peer-reviewed)abstract
- The major objectives of this paper are: (1) to review the pros and cons of the scenarios of past anthropogenic land cover change (ALCC) developed during the last ten years, (2) to discuss issues related to pollen-based reconstruction of the past land-cover and introduce a new method, REVEALS (Regional Estimates of VEgetation Abundance from Large Sites), to infer long-term records of past land-cover from pollen data, (3) to present a new project (LANDCLIM: LAND cover – CLIMate interactions in NW Europe during the Holocene) currently underway, and show preliminary results of REVEALS reconstructions of the regional land-cover in the Czech Republic for five selected time windows of the Holocene, and (4) to discuss the implications and future directions in climate and vegetation/land-cover modeling, and in the assessment of the effects of human-induced changes in land-cover on the regional climate through altered feedbacks. The existing ALCC scenarios show large discrepancies between them, and few cover time periods older than AD 800. When these scenarios are used to assess the impact of human land-use on climate, contrasting results are obtained. It emphasizes the need for methods such as the REVEALS model-based land-cover reconstructions. They might help to fine-tune descriptions of past land-cover and lead to a better understanding of how long-term changes in ALCC might have influenced climate. The REVEALS model is demonstrated to provide better estimates of the regional vegetation/landcover changes than the traditional use of pollen percentages. This will achieve a robust assessment of land cover at regional- to continental-spatial scale throughout the Holocene. We present maps of REVEALS estimates for the percentage cover of 10 plant functional types (PFTs) at 200 BP and 6000 BP, and of the two open-land PFTs “grassland” and “agricultural land” at five time-windows from 6000 BP to recent time. The LANDCLIM results are expected to provide crucial data to reassess ALCC estimates for a better understanding of the land suface-atmosphere interactions.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Huusko, Johanna M, et al.
(author)
-
Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.
- 2018
-
In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 14:7
-
Journal article (peer-reviewed)abstract
- Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, possibly damaging, nucleotide variants in mothers from families with recurrent spontaneous preterm births (SPTB). DNA samples from 17 Finnish mothers who delivered at least one infant preterm were subjected to whole exome sequencing. All mothers were of northern Finnish origin and were from seven multiplex families. Additional replication samples of European origin consisted of 93 Danish sister pairs (and two sister triads), all with a history of a preterm delivery. Rare exonic variants (frequency <1%) were analyzed to identify genes and pathways likely to affect SPTB susceptibility. We identified rare, possibly damaging, variants in genes that were common to multiple affected individuals. The glucocorticoid receptor signaling pathway was the most significant (p<1.7e-8) with genes containing these variants in a subgroup of ten Finnish mothers, each having had 2-4 SPTBs. This pathway was replicated among the Danish sister pairs. A gene in this pathway, heat shock protein family A (Hsp70) member 1 like (HSPA1L), contains two likely damaging missense alleles that were found in four different Finnish families. One of the variants (rs34620296) had a higher frequency in cases compared to controls (0.0025 vs. 0.0010, p = 0.002) in a large preterm birth genome-wide association study (GWAS) consisting of mothers of general European ancestry. Sister pairs in replication samples also shared rare, likely damaging HSPA1L variants. Furthermore, in silico analysis predicted an additional phosphorylation site generated by rs34620296 that could potentially affect chaperone activity or HSPA1L protein stability. Finally, in vitro functional experiment showed a link between HSPA1L activity and decidualization. In conclusion, rare, likely damaging, variants in HSPA1L were observed in multiple families with recurrent SPTB.
|
|
| 10. |
|
|
