A genome‐wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32

Abstract

A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 × 10(-5)) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population.

A genome-wide screen for acrophobia susceptibility loci in a Finnish isolate

“…It has previously been associated with bipolar disorder242526 and schizophrenia27. However, in our samples of acrophobia with comorbid schizophrenia (LOD = 0.51) and pure schizophrenia (LOD = 0.00) this region did not provide evidence for linkage.…”

Fine‐mapping scan of bipolar disorder susceptibility loci in Latino pedigrees

“…We previously reported significant linkage peaks at 8q24 and 14q32, and a third suggestive locus at 2q12‐q14 (Gonzalez et al, ), in the largest BD linkage study conducted in persons of Latin American ancestry to date. In this current study, we report the fine‐scale mapping of the 8q24, 14q32, and 2q12‐q14 regions in this same dataset, based on joint linkage and association analyses, to determine the specific genes or SNPs in these regions which are most likely to be associated with BD in these families.…”

“…Subjects came from families that had had at least two persons with hospital or outpatient clinic diagnoses of BD Type I or schizoaffective disorder, bipolar type. Original recruitment criteria have been previously described (Gonzalez et al, ). The sample consists exclusively of Latinos of Mexican and Central American ancestry from 416 families recruited from the eight collection sites in the United States (San Antonio, TX; El Paso, TX; Los Angeles, CA; Albuquerque, NM), Mexico (Mexico City; Monterrey) and Central America (Costa Rica; Guatemala).…”

“…Additional information was collected for each family member using the Family Interview for Genetic Studies (FIGS; Maxwell, ). Final diagnoses were determined through a best estimation process as previously described (Gonzalez et al, ). Best estimate diagnoses were made blind to any diagnoses of relatives or other family members.…”

Neuropsychiatric genetics in developing countries: Current challenges

“…Replicability of genetic findings is notoriously difficult and replicability across populations is needed to identify "genuine" genetic associations [7] . Few examples of genetic studies of NPDs and related endophenotypes in LIMCs are found, in a global perspective; some led by local scientists and others led by researchers from developed countries [8][9][10][11][12][13][14][15][16] . Research in mental health is a challenging task in LMICs [17] due to lack of resources and trained personnel.…”