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Genomic analysis of the natural history of attention-deficit/hyperactivity disorder using Neanderthal and ancient Homo sapiens samples.

ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is an impairing neurodevelopmental condition highly prevalent in current populations. Several hypotheses have been proposed to explain this paradox, mainly in the context of the Paleolithic versus Neolithic cultural shift but especially within the framework of the mismatch theory. This theory elaborates on how a particular trait once favoured in an ancient environment might become maladaptive upon environmental changes. However, given the lack of genomic data available for ADHD, these theories have not been empirically tested. We took advantage of the largest GWAS meta-analysis available for this disorder consisting of over 20,000 individuals diagnosed with ADHD and 35,000 controls, to assess the evolution of ADHD-associated alleles in European populations using archaic, ancient and modern human samples. We also included Approximate Bayesian computation coupled with deep learning analyses and singleton density scores to detect human adaptation. Our analyses indicate that ADHD-associated alleles are enriched in loss of function intolerant genes, supporting the role of selective pressures in this early-onset phenotype. Furthermore, we observed that the frequency of variants associated with ADHD has steadily decreased since Paleolithic times, particularly in Paleolithic European populations compared to samples from the Neolithic Fertile Crescent. We demonstrate this trend cannot be explained by African admixture nor Neanderthal introgression, since introgressed Neanderthal alleles are enriched in ADHD risk variants. All analyses performed support the presence of long-standing selective pressures acting against ADHD-associated alleles until recent times. Overall, our results are compatible with the mismatch theory for ADHD but suggest a much older time frame for the evolution of ADHD-associated alleles compared to previous hypotheses.

SUBMITTER: Esteller-Cucala P

PROVIDER: S-EPMC7248073 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Genomic analysis of the natural history of attention-deficit/hyperactivity disorder using Neanderthal and ancient Homo sapiens samples.

Esteller-Cucala Paula P Maceda Iago I Børglum Anders D AD Demontis Ditte D Faraone Stephen V SV Cormand Bru B Lao Oscar O

Scientific reports 20200525 1

Attention-deficit/hyperactivity disorder (ADHD) is an impairing neurodevelopmental condition highly prevalent in current populations. Several hypotheses have been proposed to explain this paradox, mainly in the context of the Paleolithic versus Neolithic cultural shift but especially within the framework of the mismatch theory. This theory elaborates on how a particular trait once favoured in an ancient environment might become maladaptive upon environmental changes. However, given the lack of g ...[more]

PMID: 32451437

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Project description:BACKGROUND:Adults with a history of childhood attention-deficit/hyperactivity disorder (ADHD) and Black drinkers are at elevated risk for alcohol problems and alcohol use disorder. Processes that increase risk for these distinct populations have not focused on in-the-moment behaviors that occur while drinking. The present study examined in-the-moment drinking characteristics (i.e., location, social context, day, time, drink type, speed of consumption) that may differ for individuals with and without ADHD histories or for Black and White drinkers. We also examined the interplay among these in-the-moment drinking characteristics to further understanding of contexts when risk may be momentarily increased. METHODS:As part of a larger study, 135 individuals (Mage = 27.81, 69.6% male, 45.9% ADHD, 69.6% White) completed a 10-day ecological momentary assessment protocol that included self-initiated reports following consumption of an alcoholic drink. Hypotheses were tested using multilevel modeling. RESULTS:Controlling for multiple demographic covariates, Black drinkers drank significantly more quickly than White drinkers and were more likely to consume hard liquor-containing beverages. Differences in drinking speed remained significant when adjusting for Black drinkers' greater likelihood to consume liquor-containing beverages and momentary experience of discrimination; however, Black drinkers' increased likelihood to consume liquor-containing beverages was no longer significant when adjusting for momentary experience of discrimination. Individuals with ADHD histories did not differ from those without ADHD histories in any in-the-moment drinking characteristics. ADHD and race did not interact to predict any drinking characteristic. CONCLUSIONS:Differences in speed of alcohol consumption and propensity to consume liquor-containing beverages may contribute to increased risk for alcohol problems experienced by Black drinkers compared to White drinkers.

Dataset Information

Genomic analysis of the natural history of attention-deficit/hyperactivity disorder using Neanderthal and ancient Homo sapiens samples.

Publications

Genomic analysis of the natural history of attention-deficit/hyperactivity disorder using Neanderthal and ancient Homo sapiens samples.

Similar Datasets

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