Discerning the ancestry of European Americans in genetic association studies

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data

Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8×10^−5), establishing a novel phenotype for this genetic variant

Genetic Differences between the Determinants of Lipid Profile Phenotypes in African and European Americans: The Jackson Heart Study

Genome-wide association analysis in populations of European descent has recently found more than a hundred genetic variants affecting risk for common disease. An open question, however, is how relevant the variants discovered in Europeans are to other populations. To address this problem for cardiovascular phenotypes, we studied a cohort of 4,464 African Americans from the Jackson Heart Study (JHS), in whom we genotyped both a panel of 12 recently discovered genetic variants known to predict lipid profile levels in Europeans and a panel of up to 1,447 ancestry informative markers allowing us to determine the African ancestry proportion of each individual at each position in the genome. Focusing on lipid profiles—HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG)—we identified the lipoprotein lipase (LPL) locus as harboring variants that account for interethnic variation in HDL-C and TG. In particular, we identified a novel common variant within LPL that is strongly associated with TG (p = 2.7×10−6) and explains nearly 1% of the variability in this phenotype, the most of any variant in African Americans to date. Strikingly, the extensively studied “gain-of-function” S447X mutation at LPL, which has been hypothesized to be the major determinant of the LPL-TG genetic association and is in trials for human gene therapy, has a significantly diminished strength of biological effect when it is found on a background of African rather than European ancestry. These results suggest that there are other, yet undiscovered variants at the locus that are truly causal (and are in linkage disequilibrium with S447X) or that work synergistically with S447X to modulate TG levels. Finally, we find systematically lower effect sizes for the 12 risk variants discovered in European populations on the African local ancestry background in JHS, highlighting the need for caution in the use of genetic variants for risk assessment across different populations

Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8×10−5), establishing a novel phenotype for this genetic variant

As and Pb and their potential source in the hair of residents of Cracow

The hair content of arsenic and lead of residents of Cracow, an agglomeration with nearly one-million population, was determined and compared to those of inhabitants of Lubasz (a village with around 3,200 population in central Poland). The sample material (composed of scalp hair samples) was collected in July and August of 2014. The residents who agreed to participate in the test had to be over eighteen years old and in the case of Cracow have been living there for at least two years. The maximum values reached 0.278 mg kg-1 arsenic and 31.7 mg kg-1 lead, and those of lead were determined in the samples collected in Lubasz. The highest mean content of arsenic (0.077 mg kg-1) was obtained for residents of Dębniki, a district of Cracow. The impact of the quality of the environment in which the tested persons lived as well as other selected factors that can affect their hair arsenic and lead content (for example: gender, age, state of health, work place, type of food, smoking, drinking) was assessed. The results have confirmed the general knowledge that a proper diet and a clean, unaffected environment are basic factors minimizing the adverse impact of arsenic and lead on human beings. The factors whose influence on the hair content of arsenic and lead were considered are: the place of residence, occupational exposure, sex, age, diet, alcohol consumption and hair colour. Due to the small number of samples that have been examined this is a pilot study

As and Pb and their potential source in the hair of residents of Cracow

The hair content of arsenic and lead of residents of Cracow, an agglomeration with nearly one -million population, was determined and compared to those of inhabitants of Lubasz (a village with around 3,200 population in central Poland). The sample material (composed of scalp hair samples) was collected in July and August of 2014. The residents who agreed to participate in the test had to be over eighteen years old and in the case of Cracow have been living there for at least two years. The maximum values reached 0.278 mg kg-1 arsenic and 31.7 mg kg-1 lead, and those of lead were determined in the samples collected in Lubasz. The highest mean content of arsenic (0.077 mg kg-1) was obtained for residents of Dębniki, a district of Cracow. The impact of the quality of the environment in which the tested persons lived as well as other selected factors that can affect their hair arsenic and lead content (for example: gender, age, state of health, work place, type of food, smoking, drinking) was assessed. The results have confirmed the general knowledge that a proper diet and a clean, unaffected environment are basic factors minimizing the adverse impact of arsenic and lead on human beings. The factors whose influence on the hair content of arsenic and lead were considered are: the place of residence, occupational exposure, sex, age, diet, alcohol consumption and hair colour. Due to the small number of samples that have been examined this is a pilot study