A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

INVESTIGATION OF BASALT-RADIONUCLIDE DISTRIBUTION COEFFICIENTS: FISCAL YEAR 1980 ANNUAL REPORT

The Basalt Waste Isolation Project (Rockwell Hanford Operations) is conducting a safety assessment of nuclear waste storage in a repository on the Hanford Site. Pacific Northwest Laboratory, in support of the assessment effort, is generating radionuclide distribution coefficient data between simulated groundwaters and basalts and their secondary mineral products under the range of physicochemical conditions expected in a repository in basalt. Experimental radionuclide distribution coefficients were determined for crushed Pomona, Flow E, and Umtanum basalts at 23°, 60°, 150°, and 300°C at both normal oxygen partial pressure (~0.2 atm) and lower oxygen partial pressure (~10{sup -7} atm), using a static technique. Little or no changes in distribution coefficients were noted for selenium, uranium, technetium, neptunium, or plutonium over the oxygen partial pressure range noted above. Sodium dithionite and hydrazine are now under study as system additives to lower Eh to -0.3 to -0.5 V, the conditions expected to prevail in the closed repository in basalt. Radium, strontium, cesium, and americium are not expected to change oxidation states under repository conditions, while iodine remains an anion in either oxidation state. Lowering the system Eh to the -0.3 to -0.5 V expected in a repository in basalt should result in an oxidation state change and enhanced removal from solution for selenium, uranium, technetium, neptunium, and plutonium. Sorption of iodine was not affected by the Eh changes. Temperature change effects on most radionuclide distribution coefficient (Kd) values over the 23° to 300°C range were major with the exception of iodine and technetium, neither of which were appreciably sorbed at normal to ~10{sup -7} atm oxygen partial pressure. Uranium Kd values increased with an increase in temperature. In addition, uranium Kd values at 23°C decrease by an order of magnitude in response to added CO{sub 3}{sup 2-} in the solution. Cesium basalt Kd values decreased from 23° to 150°C and increased from 150° to 300°C. Americium and plutonium Kd values increased from 100 to 200 ml/g at 23°C to several thousand ml/g at 150°C. Strontium Kd values reacted to temperature increases in an individualistic response that apparently depended upon the basalt contacted. Flow E basalt showed little strontium Kd change between 23° and 150°C, while an order of magnitude strontium Kd increase was noted for Umtanum basalt over the same temperature range. Selenium Kd values increased from ~5 ml/g at 23°C to 100 ml/g at 150°C. The effect of radionuclide concentration on the Kd value was shown graphically for cesium and strontium over a range of from 1 x 10{sup -10} or 10{sup -12} to 1 x 10{sup -4}M. Molarity was plotted versus Kd on log scales. The Kd values remained linear with increasing cesium or strontium concentration until ~12 x 10{sup -7} concentration were attained. Above 1 x 10{sup -7}, the Kd values decreased. When the natural log of equilibrium solution concentration (moles/liter) was plotted versus the natural log of equilibrium solids loading (moles/gram) the strontium sorption data were linearized in a Freundlich plot. The cesium sorption data, on the other hand, were linearized by the Dubinin-Radushkevich relationship. The use of {sup 99}Tc to study technetium concentration effects on sorption was unsuccessful. Technetium-95m will be utilized for this purpose in the future. Initial work was begun on Kd values obtained under controlled Eh and pH conditions to simulate specific oxygen partial pressure and pH conditions expected to occur in the repository environment. Eh values from +0.60 to -0.55 V and pH values of ~6 to 10 are expected over a period of time in the repository. Hydrazine and sodium dithionite are under investigation for use in Eh control at the lower end of the Eh range and quinhydrone for intermediate Eh range. The upper end of the pH range also can be duplicated with hydrazine and the lower end with sodium dithionite

INVESTIGATION OF BASALT-RADIONUCLIDE DISTRIBUTION COEFFICIENTS: FISCAL YEAR 1980 ANNUAL REPORT

The Basalt Waste Isolation Project (Rockwell Hanford Operations) is conducting a safety assessment of nuclear waste storage in a repository on the Hanford Site. Pacific Northwest Laboratory, in support of the assessment effort, is generating radionuclide distribution coefficient data between simulated groundwaters and basalts and their secondary mineral products under the range of physicochemical conditions expected in a repository in basalt. Experimental radionuclide distribution coefficients were determined for crushed Pomona, Flow E, and Umtanum basalts at 23°, 60°, 150°, and 300°C at both normal oxygen partial pressure (~0.2 atm) and lower oxygen partial pressure (~10{sup -7} atm), using a static technique. Little or no changes in distribution coefficients were noted for selenium, uranium, technetium, neptunium, or plutonium over the oxygen partial pressure range noted above. Sodium dithionite and hydrazine are now under study as system additives to lower Eh to -0.3 to -0.5 V, the conditions expected to prevail in the closed repository in basalt. Radium, strontium, cesium, and americium are not expected to change oxidation states under repository conditions, while iodine remains an anion in either oxidation state. Lowering the system Eh to the -0.3 to -0.5 V expected in a repository in basalt should result in an oxidation state change and enhanced removal from solution for selenium, uranium, technetium, neptunium, and plutonium. Sorption of iodine was not affected by the Eh changes. Temperature change effects on most radionuclide distribution coefficient (Kd) values over the 23° to 300°C range were major with the exception of iodine and technetium, neither of which were appreciably sorbed at normal to ~10{sup -7} atm oxygen partial pressure. Uranium Kd values increased with an increase in temperature. In addition, uranium Kd values at 23°C decrease by an order of magnitude in response to added CO{sub 3}{sup 2-} in the solution. Cesium basalt Kd values decreased from 23° to 150°C and increased from 150° to 300°C. Americium and plutonium Kd values increased from 100 to 200 ml/g at 23°C to several thousand ml/g at 150°C. Strontium Kd values reacted to temperature increases in an individualistic response that apparently depended upon the basalt contacted. Flow E basalt showed little strontium Kd change between 23° and 150°C, while an order of magnitude strontium Kd increase was noted for Umtanum basalt over the same temperature range. Selenium Kd values increased from ~5 ml/g at 23°C to 100 ml/g at 150°C. The effect of radionuclide concentration on the Kd value was shown graphically for cesium and strontium over a range of from 1 x 10{sup -10} or 10{sup -12} to 1 x 10{sup -4}M. Molarity was plotted versus Kd on log scales. The Kd values remained linear with increasing cesium or strontium concentration until ~12 x 10{sup -7} concentration were attained. Above 1 x 10{sup -7}, the Kd values decreased. When the natural log of equilibrium solution concentration (moles/liter) was plotted versus the natural log of equilibrium solids loading (moles/gram) the strontium sorption data were linearized in a Freundlich plot. The cesium sorption data, on the other hand, were linearized by the Dubinin-Radushkevich relationship. The use of {sup 99}Tc to study technetium concentration effects on sorption was unsuccessful. Technetium-95m will be utilized for this purpose in the future. Initial work was begun on Kd values obtained under controlled Eh and pH conditions to simulate specific oxygen partial pressure and pH conditions expected to occur in the repository environment. Eh values from +0.60 to -0.55 V and pH values of ~6 to 10 are expected over a period of time in the repository. Hydrazine and sodium dithionite are under investigation for use in Eh control at the lower end of the Eh range and quinhydrone for intermediate Eh range. The upper end of the pH range also can be duplicated with hydrazine and the lower end with sodium dithionite

Quality criteria of genetic algorithms for structure optimization

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