Loneliness, Depression, and Genetics in the Elderly: Prognostic Factors of a Worse Health Condition?

Loneliness is considered a prognostic factor for poorer health status in the elderly. It is proposed to analyze the role of loneliness in health status in terms of various factors. A total of 1747 individuals from the pilot survey of the Aging in Spain Longitudinal Study (ELES-PS) were reviewed. ELES is a cross-sectional study for collecting health variables, food habits, socioeconomic data, and cognitive and functional capacities, which was carried out on a Spanish representative sample of noninstitutionalized persons of 50 years of age or older. Moreover, since telomere shortening is associated with cellular senescence, 35 telomere-related SNPs and cognitive impairments were analyzed. The results characterize the "solos" as males of 50-60 years, who were overweight and had lower levels of hemoglobin and neutrophils. There is also an association between five SNPs related to telomere length and BDNF. A group of people with loneliness and depression was identified with poorer health and cognitive status, poorer perception of their quality of life, poorer quality of sleep, and lower physical activity. Therefore, it follows that telomeres and BDNF play a role as intermediaries between loneliness and depression and their relationship with a worse state of health.

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

Spanish allele and haplotype database for 32 X-chromosome Insertion-Deletion polymorphisms.

X-chromosome markers have been proved to be decisive both complementing and solving kinship analysis, particularly when autosomal markers are not able to produce adequate likelihood ratios between different hypothesis. On the other hand, Pereira et al., (2012) have demonstrated that 32 Insertion/Deletion (InDel) markers located on the X-Chromosome have a very important power of discrimination in human populations, being a novel tool in the forensic and population fields. So, the aim of the present work was testing the forensic and population genetic efficiency of the 32 X-InDel polymorphisms in the Spanish population, and subsequently build an allele/haplotype frequencies database. To accomplish this objective, a total of 555 samples comprising male individuals from 13 Spanish regions were analysed for the above mentioned 32 X-InDels in two independent laboratories. A pairwise FST analysis was performed in order to understand if the studied Spanish sub-populations present significant differences among them, detecting possible population substructure. Also, linkage disequilibrium analyses were computed to investigate the presence of association between markers in the Spanish population. After Bonferroni correction, the absence of significant differences among the studied regions supports a global Spanish population database. Concerning LD, besides previously reported linked markers MID356-MID357 and MID3690-MID3719-MID2089, we also detected significant association between MID3703-MID3774, even after Bonferroni correction. Finally, after computing allele and haplotype frequencies, forensic efficiency parameters were calculated (PDmales = 99.999976 %; PDfemales = 99.99999999998 %). Mean exclusion chance values for duos were 0.999 and trios 0.99999. These results reinforce the suitability of the 32 X-InDels marker set both in identification and kinship studies.

Kinship analysis and allelic dropout: a forensic approach on an archaeological case.

BACKGROUND: This study relies on the discovery of two pit burials (LTA and LTB) of the Bronze Age Cogotas I archaeological culture (circa 3600-2950 BP) in Spain. LTA was a single burial and LTB contained three skeletal remains of two adults and a newborn or foetus at term. AIM: The central question posed by this find was whether the LTB tomb constituted a traditional nuclear family (father, mother and son or daughter). METHODS: Ancient and forensic DNA protocols were employed to obtain reliable results. Autosomal, X-STR markers and mitochondrial DNA were amplified. Subsequently, different kinship probabilities were estimated by means of LR values calculated using the Familias 3 software. Furthermore, an allelic dropout sensitivity test was developed in order to evaluate the influence of allelic dropout phenomena on the results. RESULTS: It was possible to determine the molecular sex of all individuals and to establish a maternal relationship between the perinatal individual and one of the adults. CONCLUSION: The remains in the LTB tomb were not a traditional nuclear family (father, mother and son/daughter) and it was probably a tomb where two women, one of them pregnant, were buried.

Genetic polymorphism of 15 STR loci in El Salvador.

The aim of this study was to estimate the allelic frequencies of the 15 short tandem repeat (STR) loci included in AmpFlSTRIdentifiler PCR Amplification Kit. Biological samples were obtained from 109 unrelated individuals from El Salvador. Allelic frequencies and forensic parameters were calculated. All loci showed no departure from Hardy-Weinberg equilibrium after Bonferroni correction. The obtained frequencies were compared with other previously reported population data. The multidimensional scaling plot and the neighbor-joining phylogeny supported a high native Mesoamerican contribution.

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans.

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans.

The genetic landscape of Equatorial Guinea and the origin and migration routes of the Y chromosome haplogroup R-V88.

Human Y chromosomes belonging to the haplogroup R1b1-P25, although very common in Europe, are usually rare in Africa. However, recently published studies have reported high frequencies of this haplogroup in the central-western region of the African continent and proposed that this represents a 'back-to-Africa' migration during prehistoric times. To obtain a deeper insight into the history of these lineages, we characterised the paternal genetic background of a population in Equatorial Guinea, a Central-West African country located near the region in which the highest frequencies of the R1b1 haplogroup in Africa have been found to date. In our sample, the large majority (78.6%) of the sequences belong to subclades in haplogroup E, which are the most frequent in Bantu groups. However, the frequency of the R1b1 haplogroup in our sample (17.0%) was higher than that previously observed for the majority of the African continent. Of these R1b1 samples, nine are defined by the V88 marker, which was recently discovered in Africa. As high microsatellite variance was found inside this haplogroup in Central-West Africa and a decrease in this variance was observed towards Northeast Africa, our findings do not support the previously hypothesised movement of Chadic-speaking people from the North across the Sahara as the explanation for these R1b1 lineages in Central-West Africa. The present findings are also compatible with an origin of the V88-derived allele in the Central-West Africa, and its presence in North Africa may be better explained as the result of a migration from the south during the mid-Holocene.

Genetic polymorphism of 15 STR loci in Chinese Han population from Shanghai municipality in East China.

The aim of this study was to estimate the allelic frequencies of the fifteen STRs included in AmpFlSTR(®) Identifiler(®) PCR Amplification Kit (Applied Biosystems, USA) in a sample of 186 unrelated individuals resident in Shanghai. Allelic frequencies and forensic parameters were calculated. All loci showed no departure from Hardy-Weinberg equilibrium. The obtained frequencies were compared with other previously reported population data.

A novel SNaPshot assay to detect genetic mutations related to iron metabolism.

The minisequencing method is a cost-effective tool to study single-nucleotide polymorphisms in human disease. For this reason, a novel polymerase chain reaction multiplex SNaPshot reaction has been developed that targets 10 autosomal mutations in genes, or regions near to them, reported to be involved in iron metabolism: TMPRSS6, TF, and HFE. To validate this multiplex, 284 samples from unrelated women from the Spanish population were tested at a fertile age. The novel polymerase chain reaction multiplex SNaPshot reaction developed is a very simple, sensitive, and low-cost approach, and therefore will be useful as a tool of clinic diagnosis in iron metabolism alterations and to replicate results obtained from genome-wide linkage analysis.

CYP2C9 polymorphism in five autochthonous population of the same geographic area (Spanish Pyrenees).

OBJECTIVE: To evaluate the frequency of CYP2C9 polymorphisms in a cohort of Caucasians (Spanish Pyrenees), previously classified in autochthonous populations. METHODS: Blood samples from 154 anonymous volunteer donors were collected. All the individuals were autochthonous to their respective populations (four grandparents born in the region): 23 from Valle de Arán (Lérida), 29 from Alto Urgel (Lérida), 32 from La Cerdaña (Gerona), 30 from Jacetania (Huesca) and 40 from Cinco Villas (Navarra). The analyses for allelic mutation, CYP2C9*2 and CYP2C9*3, were identified with Taqman Allelic Discrimination kits. RESULTS: No statistical differences were found when allelic frequencies in the five autochthonous populations were compared. Frequency distribution of genotypic classes (wt/wt, wt/mut and mut/mut) in Alto Urgel was different from that in La Cerdaña, Cinco Villas and Jacetania samples. Comparison of Pyrenean and other European populations through exact test revealed significant differences in the distribution of genotypic classes: Alto Urgel, Barcelona, and Croatia yielded the highest significant differences. According to the exact test these populations were pooled in four groups. This classification produced a statistically significant percentage of variation explained by differences among groups (1.94%, P= 0.036), but not by differences among populations within groups (P=0.914), although most of the percentage of variance is explained by differences within populations (97.46%, P<0.001). CONCLUSION: This study increases the evidence of intra-population genotypic variability and highlights the significant genotypic heterogeneity when different autochthonous populations are considered, despite no clear differences in allelic frequencies do exist.

Y-chromosome haplotypes defined by 17 STRs included in AmpFlSTR Yfiler PCR Amplification Kit in a multi ethnical population from El Beni Department (North Bolivia).

Seventeen Y-STRs included in AmpFlSTR Yfiler PCR Amplification Kit (Applied Biosystems, USA) were studied in males from a multi ethnical population from El Beni Department (North Bolivia). Haplotypic and allelic frequencies were reported. Comparison of El Beni population with other samples from the region was carried out through Multidimensional Scalling over Rst distances matrix.

Identifying genetic traces of historical expansions: Phoenician footprints in the Mediterranean.

The Phoenicians were the dominant traders in the Mediterranean Sea two thousand to three thousand years ago and expanded from their homeland in the Levant to establish colonies and trading posts throughout the Mediterranean, but then they disappeared from history. We wished to identify their male genetic traces in modern populations. Therefore, we chose Phoenician-influenced sites on the basis of well-documented historical records and collected new Y-chromosomal data from 1330 men from six such sites, as well as comparative data from the literature. We then developed an analytical strategy to distinguish between lineages specifically associated with the Phoenicians and those spread by geographically similar but historically distinct events, such as the Neolithic, Greek, and Jewish expansions. This involved comparing historically documented Phoenician sites with neighboring non-Phoenician sites for the identification of weak but systematic signatures shared by the Phoenician sites that could not readily be explained by chance or by other expansions. From these comparisons, we found that haplogroup J2, in general, and six Y-STR haplotypes, in particular, exhibited a Phoenician signature that contributed > 6% to the modern Phoenician-influenced populations examined. Our methodology can be applied to any historically documented expansion in which contact and noncontact sites can be identified.

Population data for 15 Y-chromosome STRs in a population sample from Quito (Ecuador).

Population frequencies for the 9 Y-STR loci included in the "minimal haplotype" from Y-STR Haplotype Reference Database (YHRD), plus other 6 Y-STRs (DYS437, DYS438, DYS439, GATA A7.2, GATA H4 and GATA A10) were obtained for a sample of 120 males from Quito (Ecuador). One hundred and sixteen unique haplotypes were identified within the sample. Haplotype diversity (0.9994) was among the highest in comparison to other populations from Iberia and South-America. Genetic distances were calculated and our sample presented significative differences with all other samples, the lowest values being with a Guinean sample.

Genetic variability of 16 Y-chromosome STRs in a sample from Equatorial Guinea (Central Africa).

Nine Y-STR loci from the "minimal haplotype" included in Y-STR Haplotype Reference Databases (YHRD) together with eight additional Y-STRs (DYS437, DYS438, DYS439, DYS460, DYS461, GATA C4, GATA H4 and GATA A10) were analyzed in a sample of 101 males from Equatorial Guinea living in Madrid. Haplotype and allelic frequencies were calculated and genetic diversities were estimated for each genetic system as well as for the whole haplotype. An unexpected high frequency (6%) of intermediate alleles (13.2 and 14.2) was found in DYS385. For DYS19, two alleles were found in one sample. Another sample failed to amplify with DYS393 primers using either PowerPlex Y System (Promega Corporation) or the Y-PLEXtrade mark 12 (Reliagene, New Orleans, LA) commercial kits. Comparison between Equatorial Guinea and another African population (Mozambique; South East Coast) revealed a significant pairwise Phi(st) value between them (Phi(st)=0.03309; P=0.00000).

Early population differentiation in extinct aborigines from Tierra del Fuego-Patagonia: ancient mtDNA sequences and Y-chromosome STR characterization.

Ancient mtDNA was successfully recovered from 24 skeletal samples of a total of 60 ancient individuals from Patagonia-Tierra del Fuego, dated to 100-400 years BP, for which consistent amplifications and two-strand sequences were obtained. Y-chromosome STRs (DYS434, DYS437, DYS439, DYS393, DYS391, DYS390, DYS19, DYS389I, DYS389II, and DYS388) and the biallelic system DYS199 were also amplified, Y-STR alleles could be characterized in nine cases, with an average of 4.1 loci per sample correctly typed. In two samples of the same ethnic group (Aonikenk), an identical and complete eight-loci haplotype was recovered. The DYS199 biallelic system was used as a control of contamination by modern DNA and, along with DYS19, as a marker of American origin. The analysis of both mtDNA and Y-STRs revealed DNA from Amerindian ancestry. The observed polymorphisms are consistent with the hypothesis that the ancient Fuegians are close to populations from south-central Chile and Argentina, but their high nucleotide diversity and the frequency of single lineages strongly support early genetic differentiation of the Fuegians through combined processes of population bottleneck, isolation, and/or migration, followed by strong genetic drift. This suggests an early genetic diversification of the Fuegians right after their arrival at the southernmost extreme of South America.