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Team Taps Electronic Medical Records to Find Neanderthal Alleles Influencing Human Traits, Disease

NEW YORK (GenomeWeb) – A new Science study is highlighting modern human traits and conditions that appear to be influenced by introgressed Neanderthal alleles that have persisted in many human populations.

A Vanderbilt University- and University of Washington-led team used anonymized electronic medical records from the Electronic Medical Records and Genomics (eMERGE) network to ascertain phenotypes for tens of thousands of individuals of European ancestry, focusing on around 1,000 traits that could be gleaned from these files.

Results from the analyses uncovered apparent ties between Neanderthal variants that entered the human genome through mixing with Neanderthals after modern humans' out-of-Africa migration and a range of immune-, neurological-, psychiatric-, and skin-related traits or diseases.

"We discovered associations between Neanderthal DNA and a wide range of traits, including immunological, dermatological, neurological, psychiatric and reproductive diseases," corresponding author and co-senior author John Capra, a genetics researcher at Vanderbilt University, said in a statement.

In a pair of studies published earlier this year in the American Journal of Human Genetics, independent research teams used selection and archaic hominin sequence introgression patterns to identify Neanderthal sequences involved in human innate immune genes.

For their new analysis, the researchers turned to the eMERGE network to look for clues to roughly 1,000 phenotypes, using information on individual's clinical histories and treatment information.

The team focused on 28,416 de-identified, genotyped individuals from Vanderbilt's BioVU database and databases at several other American hospitals: a discovery group that included 13,686 individuals and a replication group with 14,730 individuals.

After tweaking Neanderthal haplotypes described previously using information from the Altai Neanderthal genome and human sequence data from the 1000 Genomes Project, the researchers defined roughly 135,000 SNPs suspected of stemming from Neanderthal introgression.

Starting with a genome-wide complex trait analysis, they scrutinized a subset of 1,495 common, genotyped "Neanderthal SNPs" to estimate their effects on 46 of the most common phenotypes in the eMERGE databases.

The search suggested that apparent archaic hominin variants were linked to higher-than-usual risk of depression, heart attack, and corns or calluses in the discovery group, for example. And the team saw more subtle potential associations with nine more conditions — from obesity and atherosclerosis of the heart to skin conditions.

The researchers verified eight of the 12 associations using data from the validation cohort before taking a closer look at specific SNPs that seemed to bump up or notch back risk for each of the conditions or traits considered.

The team narrowed in further on Neanderthal SNPs with apparent ties to modern human traits or maladies when it used a phenome-wide association study to look for associations involving individual SNPs.

From the 1,152 phenotypes and 1,495 Neanderthal SNPs included in a meta-analysis of individuals from both cohorts, the researchers identified Neanderthal-originating variants with apparent effects on blood coagulation and inflammation; malnutrition and/or metabolism; urinary tract disorders and bladder function; and tobacco use disorder.

Overall, the group noted, Neanderthal variant associations appeared to be overrepresented for neurologic, psychiatric, genitourinary, and other phenotypes, with less frequent links to digestive traits or heart-related conditions — patterns supported by the team's analysis of available expression quantitative trait loci (eQTL) data, which hinted at a role for Neanderthal SNPs in influencing gene expression in some brain regions.

Based on these and other findings, the researchers speculated that some Neanderthal alleles that were beneficial to modern humans making their first forays into environments outside of Africa may have less desirable effects in our current environment.

Though they conceded that more traits and conditions related to Neanderthal sequences may remain undiscovered, study's authors suggested it may be possible to unravel additional consequences of archaic introgression as analytic approaches, EMR information, and genome sequence data availability improve.