Positive selection acts on regulatory genetic variants in populations of European ancestry that affect ALDH2 gene expression.

ALDH2 is a key enzyme in alcohol metabolism that protects cells from acetaldehyde toxicity. Using iHS, iSAFE and FST statistics, we identified regulatory acting variants affecting ALDH2 gene expression under positive selection in populations of European ancestry. Several SNPs (rs3184504, rs4766578, rs10774625, rs597808, rs653178, rs847892, rs2013002) that function as eQTLs for ALDH2 in various tissues showed evidence of strong positive selection. Very large pairwise FST values indicated high genetic differentiation at these loci between populations of European ancestry and populations of other global ancestries. Estimating the timing of positive selection on the beneficial alleles suggests that these variants were recently adapted approximately 3000-3700 years ago. The derived beneficial alleles are in complete linkage disequilibrium with the derived ALDH2 promoter variant rs886205, which is associated with higher transcriptional activity. The SNPs rs4766578 and rs847892 are located in binding sequences for the transcription factor HNF4A, which is an important regulatory element of ALDH2 gene expression. In contrast to the missense variant ALDH2 rs671 (ALDH2*2), which is common only in East Asian populations and is associated with greatly reduced enzyme activity and alcohol intolerance, the beneficial alleles of the regulatory variants identified in this study are associated with increased expression of ALDH2. This suggests adaptation of Europeans to higher alcohol consumption.

Unveiling the Genetic History of the Maniq, a Primary Hunter-Gatherer Society.

The Maniq of southern Thailand is one of the last remaining practicing hunter-gatherer communities in the world. However, our knowledge on their genetic origins and demographic history is still largely limited. We present here the genotype data covering ∼2.3 million single nucleotide polymorphisms of 11 unrelated Maniq individuals. Our analyses reveal the Maniq to be closely related to the Semang populations of Malaysia (Malay Negritos), who altogether carry an Andamanese-related ancestry linked to the ancient Hòabìnhian hunter-gatherers of Mainland Southeast Asia (MSEA). Moreover, the Maniq possess ∼35% East Asian-related ancestry, likely brought about by recent admixture with surrounding agriculturist communities in the region. In addition, the Maniq exhibit one of the highest levels of genetic differentiation found among living human populations, indicative of their small population size and historical practice of endogamy. Similar to other hunter-gatherer populations of MSEA, we also find the Maniq to possess low levels of Neanderthal ancestry and undetectable levels of Denisovan ancestry. Altogether, we reveal the Maniq to be a Semang group that experienced intense genetic drift and exhibits signs of ancient Hòabìnhian ancestry.

[Socioeconomic determinants of mortality for very old men in Austria]. / Sozioökonomische Determinanten der Mortalität hochaltriger Männer in Österreich.

BACKGROUND: Although socioeconomic differences in the mortality of middle-aged persons is well-researched, little is known about socioeconomic inequalities in mortality in the very old population. Surveys and population census follow-up studies in this age group are associated with reliability and validity problems. OBJECTIVE: The aim of the study was to investigate, by linking statistical information from register data, to what extent differences in mortality exist among very old Austrian men by socioeconomic variables (e.g. education and income) and if these can be explained by differences in health status. MATERIAL AND METHODS: The data records on men aged 80-99 years counted in the Austrian register-based population census from 2011 were augmented by information from tax and social security data and merged with deaths in a 5-year follow-up period. Relative mortality risks were estimated by Cox regression. The health status was operationalized by the standardized level of care. RESULTS: Even in very old men significant differences in mortality exist depending on the socioeconomic status. A systematic effect was found for education and a poverty effect for income. When controlling not just for age but also for the standardized level of care, no socioeconomic disparities in mortality were observed. The higher mortality risk for less educated and low income very old men is thus a result of a poorer health status. CONCLUSION: At ages over 80 years the health status is the essential influencing factor on mortality. Measures to reduce socioeconomic disparities in mortality must therefore focus on earlier phases in life, in order to reduce the extent of care dependency among socially disadvantaged groups.

Selection in the dopamine receptor 2 gene: a candidate SNP study.

Dopamine is a major neurotransmitter in the human brain and is associated with various diseases. Schizophrenia, for example, is treated by blocking the dopamine receptors type 2. Shaner, Miller & Mintz (2004) stated that schizophrenia was the low fitness variant of a highly variable mental trait. We therefore explore whether the dopamine receptor 2 gene (DRD2) underwent any selection processes. We acquired genotype data of the 1,000 Genomes project (phase I), which contains 1,093 individuals from 14 populations. We included single nucleotide polymorphisms (SNPs) with two minor allele frequencies (MAFs) in the analysis: MAF over 0.05 and over 0.01. This is equivalent to 151 SNPs (MAF > 0.05) and 246 SNPs (MAF > 0.01) for DRD2. We used two different approaches (an outlier approach and a Bayesian approach) to detect loci under selection. The combined results of both approaches yielded nine (MAF > 0.05) and two candidate SNPs (MAF > 0.01), under balancing selection. We also found weak signs for directional selection on DRD2, but in our opinion these were too weak to draw any final conclusions on directional selection in DRD2. All candidates for balancing selection are in the intronic region of the gene and only one (rs12574471) has been mentioned in the literature. Two of our candidate SNPs are located in specific regions of the gene: rs80215768 lies within a promoter flanking region and rs74751335 lies within a transcription factor binding site. We strongly encourage research on our candidate SNPs and their possible effects.