Large Scale Genetic Research on Neuropsychiatric Disorders in African Populations is Needed

Dalvie, Shareefa; Koen, Nastassja; Duncan, Laramie; Abbo, Catherine; Akena, Dickens; Atwoli, Lukoye; Chiliza, Bonginkosi; Donald, Kirsten A.; Kinyanda, Eugene; Löchner, Christine; Nakasujja, Noeline; Newton, Charles R.; Ramesar, Raj; Sibeko, Goodman; Teferra, Solomon; Stein, Dan J.

doi:10.1016/j.ebiom.2015.10.002

Cited by 32 publications

(31 citation statements)

References 10 publications

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“…57 As others have noted, there are major limitations in our knowledge of the genetic and environmental risk architecture of psychiatric disorders in persons of African descent. 58 Our findings provide further evidence of the need to invest in research that includes diverse ancestral populations, to expand reference data, and to continue to develop methods to analyze data from such populations. Until such an investment is made, we are limited in our ability to understand biological mechanisms, predict genetic risk, 59 and produce optimal therapy for non-European populations.…”

Section: Discussionmentioning

confidence: 64%

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

Nievergelt

Klengel

et al. 2018

Preprint

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Post-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD following trauma is heritable, but robust common variants have yet to be identified by genome-wide association studies (GWAS). We have collected a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls. We first demonstrate significant genetic correlations across 60 PTSD cohorts to evaluate the comparability of these phenotypically heterogeneous studies. In this largest GWAS meta-analysis of PTSD to date we identify a total of 6 genome-wide significant loci, 4 in European and 2 in African-ancestry analyses. Follow-up analyses incorporated local ancestry and sex-specific effects, and functional studies. Along with other novel genes, a non-coding RNA (ncRNA) and a Parkinson's Disease gene, PARK2, were associated with PTSD. Consistent with previous reports, SNP-based heritability estimates for PTSD range between 10-20%. Despite a significant shared liability between PTSD and major depressive disorder, we show evidence that some of our loci may be specific to PTSD. These results demonstrate the role of genetic variation contributing to the biology of differential risk for PTSD and the necessity of expanding GWAS beyond European ancestry.Comparability of PGC2 studies PGC2 compiled the largest collection of global PTSD GWAS to date, with subjects recruited from both clinically deeply characterized, small patient groups and large cohorts with self-reported PTSD symptoms. We did not restrict the type of trauma subjects were exposed to, and trauma included both civilian and/or military events, often with pre-existing exposure to childhood trauma. To evaluate the comparability of these phenotypically heterogeneous studies we first estimated genetic correlations with LDSC, 15 a method that leverages GWAS summary results, the only data type available to PGC-PTSD for several of the larger military and non-US cohorts. We found significant genetic correlations (r g ) between studies using a cross-validation approach including all PGC2 EUA subjects (10 runs with studies randomly placed into 2 groups; mean r g = 0.56, mean SE = 0.23, mean p = 0.029, Supplementary Table 8).Next, additional analyses on the UK Biobank cohort (UKBB) were performed. This cohort comprises a very large proportion of the data, with almost as many EUA cases as the rest of the EUA PGC2 combined (referred to as PGC1.5). PTSD screening in UKBB was based on self-reported symptoms from a mental health survey. 16 We found a considerable genetic correlation between the UKBB and PGC1.5 EUA subjects (r g = 0.73, SE = 0.21, p = 0.0005; Supplementary Table 9). Further, sensitivity analyses in the UKBB using 3 alternative inclusion criteria for PTSD cases and controls showed stable correlations with PGC1.5 (P1 -P3; r g = 0.72 -0.79; Supplementary Table 10). Subsequent analyses were based on the UKBB phenotype including the largest number of subjects (P1; N = 126,188). Sex-stratified genetic correlations support the findings of a significant genetic signal...

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Section: Discussionmentioning

confidence: 64%

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

Nievergelt

Klengel

et al. 2018

Preprint

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“…Populations from Africa have the greatest genomic diversity and phenotypic variation among humans, with approximately 20% more genetic variants than European ancestry populations. However, evidence on the genetics of NDDs has largely relied on samples of European ancestry, creating concerns about the informativeness of the science and about global health equity (Dalvie et al, 2015). Studies exploring the genetics of NDDs in Africa have been small in scale (Abubakar et al, 2016 and references therein), and we still know relatively little about the phenotypic characteristics of these disorders in an African context.…”

Section: Rationale and Backgroundmentioning

confidence: 99%

The NeuroDev Study: Phenotypic and Genetic Characterization of Neurodevelopmental Disorders in Kenya and South Africa

Menil

Hoogenhout

Kipkemoi

et al. 2019

Neuron

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“…Furthermore, populations of African ancestry are substantially under-represented in global research of neuropsychiatric genetics. [4][5][6] From a scientific perspective, the study of modern African genomes might provide key insights into gene discovery and mapping of disease-associated variants. 7,8 The genetics of African populations, which feature increased allelic variability and reduced linkage disequilibrium compared with European populations, might reveal the missing layer of human variation that arose between 100 000 and 5 million years ago.…”

Section: Advancing Neuropsychiatric Genetics Training and Collaboratimentioning

confidence: 99%

Advancing neuropsychiatric genetics training and collaboration in Africa

Merwe

Mwesiga

McGregor

et al. 2018

The Lancet Global Health

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Large Scale Genetic Research on Neuropsychiatric Disorders in African Populations is Needed

Cited by 32 publications

References 10 publications

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

The NeuroDev Study: Phenotypic and Genetic Characterization of Neurodevelopmental Disorders in Kenya and South Africa

Advancing neuropsychiatric genetics training and collaboration in Africa

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