Differences in disease burdens across human populations are governed more by neutral evolution than by natural selection DOI Creative Commons
Ujani Hazra, Joseph Lachance

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 14, 2021

Abstract The prevalence of most complex diseases varies across human populations, and a combination socioeconomic biological factors drives these differences. Likewise, divergent evolutionary histories can lead to different genetic architectures disease, where allele frequencies linkage disequilibrium patterns at disease-associated loci differ global populations. However, it is presently unknown how much natural selection contributes the health inequities polygenic diseases. Here, we focus on ten hereditary with largest disease burden in terms mortality rates (e.g., coronary artery stroke, type 2 diabetes, lung cancer). Leveraging multiple GWAS risk scores for each examine signatures acting sets variants. First, species level, find that genomic regions associated are enriched background selection. Second, tests adaptation incorporating demographic continental super-populations indicate primarily governed by neutral evolution. Third, finer scale, testing recent positive population level. We even though some have undergone (extreme values integrated haplotype scores), not when compared baseline distributions control SNPs. Collectively, has had negligible role driving differences between These consistent late age onset many

Language: Английский

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men DOI Creative Commons
Rohini Janivara, Ujani Hazra, Aaron Pfennig

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 15, 2024

Abstract Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics male pattern baldness comes from individuals European descent. Here, we examined novel dataset comprising 2,136 men Ghana, Nigeria, Senegal, and South Africa that were genotyped using custom array. We first tested how genetic predictions generalize Europe to Africa, finding polygenic scores GWAS yielded AUC statistics ranged 0.513 0.546, indicating in African populations performed notably worse than populations. Subsequently, conducted androgenetic alopecia, focusing on self-reported patterns at age 45. After correcting for present age, population structure, study site, identified 266 moderately significant associations, 51 which independent (p-value < 10 -5 , r 2 0.2). Most associations autosomal, X chromosomes does not appear have large impact men. Finally, evolutionary causes continental differences architecture. Although Neanderthal alleles previously been associated with skin hair phenotypes, did find evidence European-ascertained hits enriched signatures ancient introgression. loci are evolving neutrally. multiple baldness-associated SNPs near EDA2R AR genes allele frequency between continents. Collectively, findings illustrate history contributes limited portability across ancestries.

Language: Английский

Citations

0
Assessing the genetic contribution of cumulative behavioral factors associated with longitudinal type 2 diabetes risk highlights adiposity and the brain-metabolic axis DOI Creative Commons
Nuno R. G. Carvalho, Yixuan He, Patrick Smadbeck

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 31, 2024

While genetic factors, behavior, and environmental exposures form a complex web of interrelated associations in type 2 diabetes (T2D), their interaction is poorly understood. Here, using data from ~500K participants the UK Biobank, we identify determinants "polyexposure risk score" (PXS) new factor that consists an accumulation 25 associated individual-level behaviors factors predict longitudinal T2D incidence. PXS-T2D had non-zero heritability (h

Language: Английский

Citations

0
Differences in disease burdens across human populations are governed more by neutral evolution than by natural selection DOI Creative Commons
Ujani Hazra, Joseph Lachance

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 14, 2021

Abstract The prevalence of most complex diseases varies across human populations, and a combination socioeconomic biological factors drives these differences. Likewise, divergent evolutionary histories can lead to different genetic architectures disease, where allele frequencies linkage disequilibrium patterns at disease-associated loci differ global populations. However, it is presently unknown how much natural selection contributes the health inequities polygenic diseases. Here, we focus on ten hereditary with largest disease burden in terms mortality rates (e.g., coronary artery stroke, type 2 diabetes, lung cancer). Leveraging multiple GWAS risk scores for each examine signatures acting sets variants. First, species level, find that genomic regions associated are enriched background selection. Second, tests adaptation incorporating demographic continental super-populations indicate primarily governed by neutral evolution. Third, finer scale, testing recent positive population level. We even though some have undergone (extreme values integrated haplotype scores), not when compared baseline distributions control SNPs. Collectively, has had negligible role driving differences between These consistent late age onset many

Language: Английский

Citations

2