NAToRA, a relatedness-pruning method to minimize the loss of dataset size in genetic and omics analyses

Leal, Thiago P.; Furlan, Vinícius; Gouveia, Mateus H.; Duarte, Julia Maria Saraiva; Fonseca, Pablo A S; Tou, Rafael; Scliar, Marília de Oliveira; Araújo, Gilderlanio Santana de; Costa, Lucas Ferrari da; Zolini, Camila; Peixoto, Maria Gabriela Campolina Diniz; Carvalho, Maria Raquel Santos; Lima‐Costa, Maria Fernanda; Gilman, Robert H.; Tarazona‐Santos, Eduardo; Rodrigues, Maíra R.

doi:10.1016/j.csbj.2022.04.009

Cited by 12 publications

(7 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, we removed individuals with missing covariates and variants that are: (i) located in structural variants using TriTyper [33], (ii) duplicated, (iii) monomorphic, (iv) potential probe sites (defined as variants in which the probe may have variable affinity due to the presence of other SNPs within 20 bp and with MAF above 1%), or (v) have failed the Hardy-Weinberg Equilibrium (HWE) exact test ( p < 10 −5 in controls). Next, we removed individuals with > 10% and variants with more than 5% of missing genetic data and inferred the relatedness between included individuals using KING [34]; those at greater than a second degree level (kinship coefficient > 0.0884) were removed using NAToRA [35] ( Figure S2 ). Unlike the Le Guen et al pipeline, samples were not removed based on ancestry.…”

Section: Methodsmentioning

confidence: 99%

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

Leal

Rao

French-Kwawu

et al. 2023

Preprint

View full text Add to dashboard Cite

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 x 10-5; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4. We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

show abstract

Section: Methodsmentioning

confidence: 99%

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

Leal

Rao

French-Kwawu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Only two related BL cases, previously reported in Uganda, 34 were identified. We used country‐specific PCs and a genetic relationship matrix (GRM), based on the probability that two individuals i and j share 0, 1, or 2 alleles identical by descent (IBD), 35 to adjust for ancestry. We fit a generalized linear mixed model, controlling for sex, age, P. falciparum detection, country, and ancestry as fixed effects, and GRM as a random variable.…”

Section: Methodsmentioning

confidence: 99%

Sickle cell allele HBB‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa

Hong,

Gouveia,

Ogwang

et al. 2023

American J Hematol

Self Cite

View full text Add to dashboard Cite

Burkitt lymphoma (BL) is an aggressive B‐cell lymphoma that significantly contributes to childhood cancer burden in sub‐Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria—such as the sickle cell trait variant, HBB‐rs334(T)—also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome‐scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB‐rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628–0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533–0.885; p = .0037). ABO‐rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379–0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.

show abstract

“…To create the subset, we selected self-reported Latin American individuals included in the Genetics of Latin American Diversity (GLAD) project [21] , as well as individuals from the Women's Health Initiative, the Jackson Heart Study, the 1KGP, the Human Genome Diversity Project, the Framingham Heart Study, the Barbados Asthma Genetics Study, and the MultiEthnic Study of Atherosclerosis (MESA) [11,[22][23][24][25][26][27] . We calculated the genetic relationship using KING [28] and excluded related individuals using NAToRA [29] . In this work, we considered individuals with third-degree (kinship coefficient > 0.0442) or higher as related.…”

Section: Data Source For Reference Panelsmentioning

confidence: 99%

“…For CUSCH-LOAD, we also created two additional plink files containing only individuals from Puerto Rico (PR) or the Dominican Republic (DR). We then ran relatedness via KING [28] to get kinship coefficients for each pair of individuals in each target population, and individuals with a third degree or closer relationship were removed using NAToRA [29] .…”

Section: Quality Control For Target Populationsmentioning

confidence: 99%

Comparing the effect of imputation reference panel composition in four distinct Latin American cohorts

French,

Pua,

Laboulaye

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Genome-wide association studies have been useful in identifying genetic risk factors for various phenotypes. These studies rely on imputation and many existing panels are largely composed of individuals of European ancestry, resulting in lower levels of imputation quality in underrepresented populations. We aim to analyze how the composition of imputation reference panels affects imputation quality in four target Latin American cohorts. We compared imputation quality for chromosomes 7 and X when altering the imputation reference panel by: 1) increasing the number of Latin American individuals; 2) excluding either Latin American, African, or European individuals, or 3) increasing the Indigenous American (IA) admixture proportions of included Latin Americans. We found that increasing the number of Latin Americans in the reference panel improved imputation quality in the four populations; however, there were differences between chromosomes 7 and X in some cohorts. Excluding Latin Americans from analysis resulted in worse imputation quality in every cohort, while differential effects were seen when excluding Europeans and Africans between and within cohorts and between chromosomes 7 and X. Finally, increasing IA-like admixture proportions in the reference panel increased imputation quality at different levels in different populations. The difference in results between populations and chromosomes suggests that existing and future reference panels containing Latin American individuals are likely to perform differently in different Latin American populations.

show abstract

NAToRA, a relatedness-pruning method to minimize the loss of dataset size in genetic and omics analyses

Cited by 12 publications

References 14 publications

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

Sickle cell allele HBB‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa

Comparing the effect of imputation reference panel composition in four distinct Latin American cohorts

Contact Info

Product

Resources

About