| 1. |
- Craddock, Nick, et al.
(author)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Journal article (peer-reviewed)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
- Bouckaert, Remco, et al.
(author)
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Mapping the Origins and Expansion of the Indo-European Language Family
- 2012
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 337:6097, s. 957-960
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Journal article (peer-reviewed)abstract
- There are two competing hypotheses for the origin of the Indo-European language family. The conventional view places the homeland in the Pontic steppes about 6000 years ago. An alternative hypothesis claims that the languages spread from Anatolia with the expansion of farming 8000 to 9500 years ago. We used Bayesian phylogeographic approaches, together with basic vocabulary data from 103 ancient and contemporary Indo-European languages, to explicitly model the expansion of the family and test these hypotheses. We found decisive support for an Anatolian origin over a steppe origin. Both the inferred timing and root location of the Indo-European language trees fit with an agricultural expansion from Anatolia beginning 8000 to 9500 years ago. These results highlight the critical role that phylogeographic inference can play in resolving debates about human prehistory.
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| 3. |
- Su, Zhan, et al.
(author)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Journal article (peer-reviewed)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 4. |
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| 5. |
- Gavin, Michael C., et al.
(author)
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Toward a Mechanistic Understanding of Linguistic Diversity
- 2013
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In: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 63:7, s. 524-535
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Journal article (peer-reviewed)abstract
- Our species displays remarkable linguistic diversity. Although the uneven distribution of this diversity demands explanation, the drivers of these patterns have not been conclusively determined. We address this issue in two steps: First, we review previous empirical studies whose authors have suggested environmental, geographical, and sociocultural drivers of linguistic diversification. However, contradictory results and methodological variation make it difficult to draw general conclusions. Second, we outline a program for future research. We suggest that future analyses should account for interactions among causal factors, the lack of spatial and phylogenetic independence of the data, and transitory patterns. Recent analytical advances in biogeography and evolutionary biology, such as simulation modeling of diversity patterns, hold promise for testing four key mechanisms of language diversification proposed here: neutral change, population movement, contact, and selection. Future modeling approaches should also evaluate how the outcomes of these processes are influenced by demography, environmental heterogeneity, and time.
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