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Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry.sup.1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific.sup.4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations.sup.11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States--where minority populations have a disproportionately higher burden of chronic conditions.sup.13--the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities. Genetic analyses of ancestrally diverse populations show evidence of heterogeneity across ancestries and provide insights into clinical implications, highlighting the importance of including ancestrally diverse populations to maximize genetic discovery and reduce health disparities., Author(s): Genevieve L. Wojcik [sup.1] , Mariaelisa Graff [sup.2] , Katherine K. Nishimura [sup.3] , Ran Tao [sup.4] [sup.5] , Jeffrey Haessler [sup.3] , Christopher R. Gignoux [sup.1] [sup.6] , [...]

The Bayash are a branch of Romanian speaking Roma living dispersedly in Central, Eastern, and Southeastern Europe. To better understand the molecular architecture and origin of the Croatian Bayash paternal gene pool, 151 Bayash Y chromosomes were analyzed for 16 SNPs and 17 STRs and compared with European Romani and non-Romani majority populations from Europe, Turkey, and South Asia. Two main layers of Bayash paternal gene pool were identified: ancestral (Indian) and recent (European). The reduced diversity and expansion signals of H1a patrilineages imply descent from closely related paternal ancestors who could have settled in the Indian subcontinent, possibly as early as between the eighth and tenth centuries AD. The recent layer of the Bayash paternal pool is dominated by a specific subset of E1b1b1a lineages that are not found in the Balkan majority populations. At least two private mutational events occurred in the Bayash during their migrations from the southern Balkans toward Romania. Additional admixture, evident in the low frequencies of typical European haplogroups, J2, R1a, I1, Rlblb2, G, and I2a, took place primarily during the early Bayash settlement in the Balkans and the Romani bondage in Romania. Our results indicate two phenomena in the Bayash and analyzed Roma: a significant preservation of ancestral H1a haplotypes as a result of considerable, but variable level of endogamy and isolation and differential distribution of less frequent, but typical European lineages due to different patterns of the early demographic history in Europe marked by differential admixture and genetic drift. Am J Phys Anthropol 138:333-342, 2009. KEY WORDS Y chromosome haplogroups; Roma; Bayash

P450 oxidoreductase (POR) is an electron-donating flavoprotein required for the activity of all microsomal cytochrome P450 enzymes. We sequenced 5,655 bp of the POR gene in a representative population of 842 healthy unrelated individuals in four ethnic groups: 218 African Americans, 260 Caucasian Americans, 179 Chinese Americans, and 185 Mexican Americans. One hundred forty SNPs were detected, of which 43 were found in [greater than or equal to] 1% of alleles. Twelve SNPs were in the POR promoter region. Fifteen of 32 exonic variations altered the POR amino acid sequence; 13 of these 15 are previously undescribed missense variations. We found eight indels, only one of which was in the coding region. A previously described variant, A503V, was found on 27.9% of all alleles with some ethnic predilection (19.1% in African Americans, 26.4% in Caucasian Americans, 36.7% Chinese Americans, and 31.0% in Mexican Americans). We built cDNA expression vectors for the 13 previously undescribed missense variants, expressed each protein lacking 27 N-terminal residues in Escherichia coil, and assayed the apparent Km and Vmax of each in four assays: reduction of cytochrome c, oxidation of NADPH, 17[alpha]-hydroxylase activity of P450c17, and 17,20 lyase activity of P450c17. The catalytic activities of several missense mutants differed substantially in these assays, indicating that each POR mutant must be assayed separately with each potential target P450 enzyme. The activity of AS03V was reduced to a modest but statistically significant degree in all four assays, suggesting that it may play an important role in inter-individual variation in drug response. cytochrome P450 | drug metabolism | electron transfer | pharmacogenomics | steroidogenesis

Across the 42 counties of Romania, the total suicide rate ann me population percentage of ethnic Hungarians were strongly positively interrelated (79% attributable variance). Counties with the strongest Hungarian minority had suicide rates converging to (or exceeding) the suicide rate for Hungary, which rate is high. Of a set of about 20 vital statistics and socioeconomic indicators, only life expectancy predicted a significant increment of further variance in the suicide rates. However, this effect was small, adding merely 3% further variance explained to 79% already accounted for. Overall, the findings are supportive of the Finno-Ugrian Suicide Hypothesis, i.e., the notion that geographic patterns of suicide prevalence may be partially due to genetic differences between populations. Supplemental analyses of a questionnaire item which specifically queried this study's main finding indicated widespread disbelief of this fact of suicide prevalence across a variety of samples, including two samples from Romania.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2005.12.014 Byline: R.Y.Y. Yong (a), L.S.H. Gan (a), M.D. Coble (b), E.P.H. Yap (a) Keywords: MiniSTR; Allele frequencies; Population data; Singapore Abstract: MiniSTR loci has demonstrated to be an effective approach to recover genetic information from degraded sample, due to the improved PCR efficiency of their reduced PCR product sizes. This study investigated the allele frequency of six miniSTR loci, D1S1677, D2S441, D4S2364, D10S1248, D14S1434 and D22S1045, in three Singapore populations. All loci showed a moderate degree of polymorphism with observed heterozygosity >0.6 for all three populations. The allele frequencies, forensic parameters and heterozygosity comparison with other CODIS STR in similar populations are presented. Author Affiliation: (a) Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, Singapore 117510, Singapore (b) National Institute of Standards and Technology, Biotechnology Division, 100 Bureau Drive, Mail Stop 8311, Gaitherburg, MD 20899, USA Article History: Received 18 October 2005; Revised 7 December 2005; Accepted 7 December 2005

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with increases in hepatic (HTG) and/or intramyocellular lipid content, little is known about the prevalence of insulin resistance and potential differences in intracellular lipid distribution among healthy, young, lean individuals of different ethnic groups. To examine this question, 482 young, lean, healthy, sedentary, nonsmoking Eastern Asians (n = 49), Asian-Indians (n = 59), Blacks (n = 48), Caucasians (n = 292), and Hispanics (n = 34) underwent an oral glucose tolerance test to assess whole-body insulin sensitivity by an insulin sensitivity index. In addition, intramyocellular lipid and HTG contents were measured by using proton magnetic resonance spectroscopy. The prevalence of insulin resistance, defined as the lower quartile of insulin sensitivity index, was [approximately equal to]2- to 3-fold higher in the Asian-Indians compared with all other ethnic groups, and this could entirely be attributed to a 3- to 4-fold increased prevalence of insulin resistance in Asian-Indian men. This increased prevalence of insulin resistance in the Asian-Indian men was associated with an [approximately equal to]2-fold increase in HTG content and plasma IL-6 concentrations compared with Caucasian men. These data demonstrate important ethnic and gender differences in the pathogenesis of insulin resistance in Asian-Indian men and have important therapeutic implications for treatment of T2DM and for the development of steatosis-related liver disease in this ethnic group. gender and ethnic differences | hepatic steatosis | insulin resistance | risk of type 2 diabetes

Although there are numerous ethnic groups in Sierra Leone, the Mende and Temne together account for approximately 60% of the total population. To see if genetic differences could be observed among ethnic groups in Sierra Leone, the nucleotide sequence of the hypervariable 1 (HV1) region of mitochondrial DNA (mtDNA) was determined from samples of the two major ethnic groups, the Mende (n = 59) and Temne (n = 121), and of two minor ethnic groups, the Loko (n = 29) and Limba (n = 67). Among these 276 HV1 sequences, 164 individual haplotypes were observed. An analysis of molecular variance indicated that the distribution of these haplotypes within the Limba sample was significantly different from that of the other ethnic groups. No significant genetic variation was seen between the Mende, Temne, and Loko. These results indicate that distinguishing genetic differences can be observed among ethnic groups residing in historically close proximity to one another. Furthermore, we observed some mitochondrial DNA haplotypes that are common among the Sierra Leone ethnic groups but that have not been observed in other published studies of West African ethnic groups. Therefore, we may have evidence for mtDNA lineages that are unique to this region of West Africa. Am J Phys Anthropol 128:156-163, 2005.

Restriction fragment length polymorphisms are good anthropological markers for discriminating geographically distinct populations at both the allele and the haplotype level. Two communities of African ancestry and ladinos, mestizos, and mulattoes living in the Esmeraldas province in northwestern Ecuador were analyzed for three RFLPs (EcoRI, RsaI, and MspI) of the COL1A2 gene. Also, the same markers were studied in a population sample from Spain to compare the allele and haplotype frequencies of the Esmeraldas populations with those of their representative European parental population. Data for the native American and sub-Saharan African founder components were available from the literature. No significant levels of differentiation between the two African Ecuadoran communities emerged from either the frequency analysis of each single marker and all three RFLP markers together or from the AMOVA. The ladinos and mestizos also showed a rather similar distribution of allele and haplotype frequencies, confirming that the two ethnic terms do not correspond to genetically different populations. The comparison with the supposed founding European, sub-Saharan African, and native American populations indicated a large presence of African genes in the gene pool of both communities, with a higher proportion of the Amerindian component in Viche than in Rio Cayapas. The present findings confirm the previous genetic admixture estimates based on nuclear and mitochondrial DNA markers and the demographic data. KEY WORDS: COL1A2, EcoRI, RsaI, MspI, ECUADORAN MIXED POPULATIONS, SPANISH POPULATION, ECUADOR., The population of Ecuador includes ethnically and genetically distinct groups besides native Americans, who make up nearly half the total population. Other groups include the ladinos, who are descended from [...]

Three historical ethnic minorities are present in Calabria: Albanians, Greeks, and Occitans. The Albanian ethnic minority is the more populous, having settled in Calabria between the 15th and 17th centuries, and these populations are now located in the provinces of Cosenza and Catanzaro. In the present study the Albanian population structure is analyzed based on the allele frequencies of six classic genetic markers: ACP, GC, PGM1, AK, ADA, and 6PGD. The results show a significant heterogeneity between the Albanian population in Calabria and the population in Molise. Therefore the cultural and reproductive isolation of the Albanian ethnic minority of Calabria is related to a great genetic peculiarity. Moreover, the frequencies of some alleles, particularly those of the PGM*1W31 variant, and the analysis of the R matrix still show the actual peculiar genetic structure of the Albanians of Calabria, although the genetic flow is evident in the decrease of endogamy and in the increase in the degree of mixing. KEY WORDS: ALBANIANS, CALABRIA, ACP, GC, PGM1, AK, ADA, 6PGD., The arrival of the Albanian population in Italy began at the end of the 14th century. The first Albanians who came to central-southern Italy were soldiers who received some Calabrian [...]

Research has been conducted on diverse ethnic population of China, where genetic differences may contribute to HIV transmission efficiency. Results demonstrate that CCR5 expression is greater in the Dai minority than in any other investigated minority.

Byline: M. A. Bermisheva (1), K. Tambets (2), R. Villems (2), E. K. Khusnutdinova (1) Keywords: mitochondrial DNA; haplotyping; ethnogenomics; ethnic groups of the Volga--Ural region Abstract: The mtDNA polymorphism was analyzed in eight ethnic groups (N = 979) of the Volga--Ural region. Most mtDNA variants belonged to haplogroups H, U, T, J, W, I, R, and N1 characteristic of West Eurasian populations. The most frequent were haplogroups H (12--42%) and U (18--44%). East Eurasian mtDNA types (A, B, Y, F, M, N9) were also observed. Genetic diversity was higher in Turkic than in Finno-Ugric populations. The frequency of mtDNA types characteristic of Siberian and Central Asian populations substantially increased in the ethnic groups living closer to the Urals, a boundary between Europe and Asia. Geographic distances, rather than linguistic barriers, were assumed to play the major role in distribution of mtDNA types in the Volga--Ural region. Thus, as concerns the maternal lineage, the Finno-Ugric populations of the region proved to be more similar to their Turkic neighbors rather than to linguistically related Balto-Finnish ethnic groups. Author Affiliation: (1) Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, 450054, Russia (2) Estonian Biological Center, Tartu University, Tartu, Estonia Article History: Registration Date: 09/10/2004

Byline: I. M. Khidiyatova (1), L. U. Dzhemileva (1), R. M. Khabibulin (2), E. K. Khusnutdinova (1) Keywords: non-syndromic recessive deafness; connexin 26; GJB2; 35delG mutation; Volga--Ural region Author Affiliation: (1) Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, 450054, Russia (2) Bashkortostan Children's Hospital, Ufa, 450092, Russia Article History: Registration Date: 09/10/2004

This article examines gene frequencies in two Costa Rican ethnic groups with similar rates of twin births. Findings indicate that there are significant differences in gene frequencies between the ethnic groups and that a similarity in twinning rates may be more influenced by environmental than genetic factors.

The mitochondrial DNA of Corsicans are examined to establish genetic patterns among the Corsicans and other ethnic groups, such as the Basques and Sardinians. Results indicate east-to-west migration fifteen to forty thousand years ago although genetic results conflict with paleontological evidence.

Use of unlinked genetic markers for detection of population stratification in association studies has been evaluated. Where there is population stratification, it can be found by using unlinked marker loci. The case-control study design where unrelated control individuals are used is a valid approach for association mapping, assuming that marker loci unlinked to the candidate locus are included in the study for testing for stratification. Guidleines for the number of unlinked marker loci to use are given.

Elevated hematocrits, which are found in many high-altitude populations, increase the oxygen-carrying capacity of blood and may represent an adaptation to hypoxic environments. However, as high hematocrit increases blood viscosity, which in turn is associated with hypertension and heart disease, it may be advantageous for high-altitude populations to limit other factors that contribute to increased blood viscosity. One such factor is the plasma concentration of the coagulation protein fibrinogen. Several common polymorphisms in the [Beta]-fibrinogen gene have been identified that affect fibrinogen concentrations. We determined the allele frequencies of three of these polymorphisms ([G/A.sup.-455](HaeIII), [C/T.sup.-148](HindIII), and [G/A.sup.+448](MnlI)) in sample groups drawn from three populations: Quechua-speaking natives living at over 3,200 m in the Peruvian Andes, North American natives (Na-Dene) from coastal British Columbia, and Caucasian North Americans. The frequencies of the alleles previously shown to be associated with increased fibrinogen levels were so low in the Quechuas that their presence could be accounted for solely by genetic admixture with Caucasians. Frequencies in the Na-Dene, a Native American group unrelated to the Quechua, were not significantly different from those in Caucasians. KEY WORDS Native Americans; altiplano; fibrinogen; hypoxia

The human populations of the Brazilian Amazon were formed by interethnic crosses between Europeans, Africans, and Amerindians. The relative contribution of men and women of different ethnic groups was not homogeneous, since the social policies of the first three centuries of Brazilian colonization encouraged mating between European men and indigenous women and, later on, African women. In order to test this model based on historical data, we compared the relative contribution of the Y-DNA and mtDNA of Amerindian and non-Amerindian populations to the formation of the urban population of the town of Belem, in the Amazon region, on the basis of a C[right arrow]T mutation at locus DYS199 present in 90% of the Amerindian Y-DNA and of five markers that define 99% of the mitochondrial sequences of Amerindians. The contribution of indigenous men to the formation of this population was less than 5%, whereas the contribution of indigenous women was estimated at more than 50% of the mitochondrial sequences of the same population. Thus, the present results demonstrate that the contribution of indigenous women to the formation of the Belem population was 10 times higher than the contribution of indigenous men, a genetic consequence of social behavior and attitudes of the past; our results also help clarify the process of integration of indigenous communities into the urban societies in Brazil and possibly in other countries. KEY WORDS Amerindians; urban populations; genetic diversity; mitochondrial DNA; Y-DNA; Amazon; polymorphisms

Sequence data from the first hypervariable segment of the mitochondrial DNA control region of 124 subjects belonging to three African-Brazilian and three Brazilian Indian populations were compared with information related to 12 protein genetic loci from 601 persons living in the same localities. There is high diversity among the mtDNA sites, and the most variable in one ethnic group are not the most variable in the other. No differences in gene diversity between populations within ethnic groups were observed, but the Indians showed a reduced variability. Much more interpopulation variation was observed in the mtDNA data than in the protein set. The relationships obtained for the six populations, however, are the same regardless whether mtDNA or protein loci are considered. African-Brazilians from Porto Alegre and Salvador, situated 3,000 km apart, are more similar to each other than both are to Paredao, despite the geographical proximity between Porto Alegre and Paredao, which are just 50 km apart. The tree topology in relation to the three Indians groups, on the other hand, is that expected when languages, culture, and geography are considered. KEY WORDS mtDNA variation; African-Brazilians; Brazilian Indians; gene diversity

Many HIV-1 infected women transmit the infection to their offspring during gestation while others do not, suggesting that nonmaternal factors and the infant's major histocompatibility complex class II DRB1 alleles are involved in the transmission process. This observation was evaluated by examining 46 HIV-infected infants and 63 seroreverting infants by the automated nucleotide-sequence-based technique. HIV-infection was not detected in infants with DR13 alleles, suggesting the nonprogression of the disease after infection. This association was particularly pronounced in ethnic groups.

In the past decade, researchers have dramatically improved our understanding of the genetic basis of complex chronic diseases, such as Alzheimer's disease and type 2 diabetes, through more than 1,000 [...]

Mexican Americans are a numerous and fast growing ethnic population in the United States. Yet little is known about their genetic structure. Since they are a hybrid, it is of interest to identify their parental populations and to estimate the relative contributions of these groups. This information is relevant to historical, biomedica, and evolutionary concerns. New genetic typings on 730 Arizona Mexican Americans for the HLA-A, HLA-B, ABO, Rh, MNSs, Duffy, Kidd, and Kell loci are presented here and they are used to estimate ancestral contributions. We considered both a dihybrid model with Amerindians and Spaniards as proposed ancestors, and a trihybrid model with Amerindians, Spaniards, and Africans as proposed ancestors. A modified weighted least squares method that allows for linkage disequilibrium was used to estimate ancestral contributions for each mode. The following admixture estimates were obtained: Amerindian, 0.20 [+ or -] 0.04; Spaniard, 0.68 [+ or -] 0.06; and African, 0.03 [+ or -] 0.02. The interpretation of these results with respect to Amerindian and Spanish ancestry is straightforward. African ancestry is strongly supported by the presence of a marker of African descent, Fy, despite the fact that the standard error of the estimate is as large as the estimated admixture proportion. An evaluation of the sensitivity of these results to a number of variables is presented: 1) our choices of ancestral allele frequencies, 2) the possibility of selection at HLA and the blood groups, and 3) genetic drift in Mexican Americans.

The Makrani of Pakistan are descended from Africans forced into slavery. The Makrani of Pakistan are descended from Africans forced into slavery., Author Affiliations: A Pakistani ethnic group traces its roots to eastern Africa Members of a Pakistani ethnic group called the Makrani are descendants of enslaved East Africans. According to the [...]

The 40-bp variable number of tandem repeats polymorphism in the 3' untranslated region of the human DAT1 (dopamine transporter 1) is studied to test the influence of geographical and linguistic affiliation on the genetic affinities among the Iranian population. The DAT1 distribution in Iran has a different pattern, which leads to an understanding of differentiation and diversity of Iranian ethnic groups.

The frequency of DRD2A1, DRD3A1, DRD4/2R-10R and 5HT2C-A1 variants in the population of the city of La Plata, Argentina, and in Amerindians from Argentina, Paraguay and Chile is reported. The analysis has suggested that the ethnic variations in the prevalence of the allelic forms of these genes might be a confounding factor to be taken into consideration in studies of association between dopaminergic and serotonergic receptor genotypes and neuropsychiatric and mood disorders.

Samples from 31 tribal populations of India were analyzed for the mitochondrial DNA 9-base-pair deletion/insertion polymorphism and characterized to test the genetic origins of the ethnically and linguistically heterogeneous Austro-Asiatic tribes of India. Results suggest multiple origins of Austro-Asiatic tribes of India, particularly the Asian and non-Asian origins of the Mon-Khmer and Mundari populations, also indicating two different waves of migration of the Mon-Khmer tribes in India.

BIDYUT ROY [1] PARTHA P. MAJUMDER [1] BADAL DEY [1] MADAN CHAKRABORTY [1] SANAT BANERJEE [1] MONAMI ROY [1] NAMITA MUKHERJEE [1] SAMIR K. SIL [2] Abstract. We estimated the [...]

ALEXANDRE C. PEREIRA [1] GLORIA F. A. MOTA [1] JOSE E. KRIEGER [1] Abstract Genetic testing for hemochromatosis may have important implications for diagnosis and screening of the disease. However, […]