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Article ; Online: Utility of blood pressure genetic risk score in admixed Hispanic samples.

Beecham, A H / Wang, L / Vasudeva, N / Liu, Z / Dong, C / Goldschmidt-Clermont, P J / Pericak-Vance, M A / Rundek, T / Seo, D / Blanton, S H / Sacco, R L / Beecham, G W

Journal of human hypertension

2016 Volume 30, Issue 12, Page(s) 772–777

Abstract: Hypertension is strongly influenced by genetic factors. Although hypertension prevalence in some Hispanic sub-populations is greater than in non-Hispanic whites, genetic studies on hypertension have focused primarily on samples of European descent. A ... ...

Abstract	Hypertension is strongly influenced by genetic factors. Although hypertension prevalence in some Hispanic sub-populations is greater than in non-Hispanic whites, genetic studies on hypertension have focused primarily on samples of European descent. A recent meta-analysis of 200 000 individuals of European descent identified 29 common genetic variants that influence blood pressure, and a genetic risk score derived from the 29 variants has been proposed. We sought to evaluate the utility of this genetic risk score in Hispanics. The sample set consists of 1994 Hispanics from 2 cohorts: the Northern Manhattan Study (primarily Dominican/Puerto Rican) and the Miami Cardiovascular Registry (primarily Cuban/South American). Risk scores for systolic and diastolic blood pressure were computed as a weighted sum of the risk alleles, with the regression coefficients reported in the European meta-analysis used as weights. Association of risk score with blood pressure was tested within each cohort, adjusting for age, age
MeSH term(s)	African Americans/genetics ; Aged ; Blood Pressure/genetics ; European Continental Ancestry Group/genetics ; Female ; Florida/epidemiology ; Genotype ; Hispanic Americans/genetics ; Humans ; Hypertension/diagnosis ; Hypertension/ethnology ; Hypertension/genetics ; Hypertension/physiopathology ; Indians, North American/genetics ; Male ; Middle Aged ; New York City/epidemiology ; Phenotype ; Polymorphism, Single Nucleotide ; Registries ; Risk Assessment ; Risk Factors
Language	English
Publishing date	2016-06-02
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Multicenter Study ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	639472-3
ISSN	1476-5527 ; 0950-9240
ISSN (online)	1476-5527
ISSN	0950-9240
DOI	10.1038/jhh.2016.29
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Zs.A 2380: Show issues

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Article ; Online: The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.

Beecham, A H / Amezcua, L / Chinea, A / Manrique, C P / Rubi, C / Isobe, N / Lund, B T / Santaniello, A / Beecham, G W / Burchard, E G / Comabella, M / Patsopoulos, N / Fitzgerald, K / Calabresi, P A / De Jager, P / Conti, D V / Delgado, S R / Oksenberg, J R / McCauley, J L

Multiple sclerosis (Houndmills, Basingstoke, England)

2019 Volume 26, Issue 11, Page(s) 1329–1339

Abstract: Background: Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the ... ...

Abstract	Background: Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States. Objective: We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex ( Methods: Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls). We conducted single variant, pathway, and cumulative genetic risk score analyses. Results: We found less replication than statistical power suggested, particularly among African Americans. This could be due to limited correlation between the tested and causal variants within the sample or alternatively could indicate allelic and locus heterogeneity. Differences were observed between pathways enriched among the replicating versus all 200 variants. Although these differences should be examined in larger samples, a potential role exists for gene-environment or gene-gene interactions which alter phenotype differentially across racial and ethnic groups. Cumulative genetic risk scores were associated with MS within each study sample but showed limited diagnostic capability. Conclusion: These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.
MeSH term(s)	Black or African American/genetics ; Alleles ; Genetic Variation ; Hispanic or Latino/genetics ; Humans ; Multiple Sclerosis/genetics ; Polymorphism, Single Nucleotide ; United States/epidemiology
Language	English
Publishing date	2019-08-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/1352458519863764
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Zs.A 4428: Show issues

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Article: Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function.

Cukier, H N / Kunkle, B K / Hamilton, K L / Rolati, S / Kohli, M A / Whitehead, P L / Jaworski, J / Vance, J M / Cuccaro, M L / Carney, R M / Gilbert, J R / Farrer, L A / Martin, E R / Beecham, G W / Haines, J L / Pericak-Vance, M A

Journal of Alzheimer's disease & Parkinsonism

2017 Volume 7, Issue 4

Abstract: Objective: Alzheimer's disease (AD) is a neurodegenerative disorder for which more than 20 genetic loci have been implicated to date. However, studies demonstrate not all genetic factors have been identified. Therefore, in this study we seek to identify ...

Abstract	Objective: Alzheimer's disease (AD) is a neurodegenerative disorder for which more than 20 genetic loci have been implicated to date. However, studies demonstrate not all genetic factors have been identified. Therefore, in this study we seek to identify additional rare variants and novel genes potentially contributing to AD. Methods: Whole exome sequencing was performed on 23 multi-generational families with an average of eight affected subjects. Exome sequencing was filtered for rare, nonsynonymous and loss-of-function variants. Alterations predicted to have a functional consequence and located within either a previously reported AD gene, a linkage peak (LOD>2), or clustering in the same gene across multiple families, were prioritized. Results: Rare variants were found in known AD risk genes including Conclusion: Utilizing large families with a heavy burden of disease allowed for the identification of rare variants co-segregating with disease. Variants were identified in both known AD risk genes and in novel genes.
Language	English
Publishing date	2017-07-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2711981-6
ISSN	2161-0460
ISSN	2161-0460
DOI	10.4172/2161-0460.1000355
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Article ; Online: Targeted sequencing of ABCA7 identifies splicing, stop-gain and intronic risk variants for Alzheimer disease.

Kunkle, B W / Carney, R M / Kohli, M A / Naj, A C / Hamilton-Nelson, K L / Whitehead, P L / Wang, L / Lang, R / Cuccaro, M L / Vance, J M / Byrd, G S / Beecham, G W / Gilbert, J R / Martin, E R / Haines, J L / Pericak-Vance, M A

Neuroscience letters

2017 Volume 649, Page(s) 124–129

Abstract: Several variants in the gene ABCA7 have been identified as potential causal variants for late-onset Alzheimer's disease (LOAD). In order to replicate these findings, and search for novel causal variants, we performed targeted sequencing of this gene in ... ...

Abstract	Several variants in the gene ABCA7 have been identified as potential causal variants for late-onset Alzheimer's disease (LOAD). In order to replicate these findings, and search for novel causal variants, we performed targeted sequencing of this gene in cohorts of non-Hispanic White (NHW) and African-American (AA) LOAD cases and controls. We sequenced the gene ABCA7 in 291 NHW LOAD cases and 103 controls. Variants were prioritized for rare, damaging variants and previously reported variants associated with LOAD, and were follow-up genotyped in 4076 NHW and 1157 AA cases and controls. We confirm three previously associated ABCA7 risk variants and extend two of these associations to other populations, an intronic variant in NHW (P=3.0×10
MeSH term(s)	ATP-Binding Cassette Transporters/genetics ; African Americans/genetics ; Alzheimer Disease/genetics ; European Continental Ancestry Group/genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Introns ; Male ; Pedigree ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA
Chemical Substances	ABCA7 protein, human ; ATP-Binding Cassette Transporters
Language	English
Publishing date	2017-04-08
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2017.04.014
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Zs.A 1166: Show issues

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Article ; Online: Genome-wide scan demonstrates significant linkage for male sexual orientation.

Sanders, A R / Martin, E R / Beecham, G W / Guo, S / Dawood, K / Rieger, G / Badner, J A / Gershon, E S / Krishnappa, R S / Kolundzija, A B / Duan, J / Gejman, P V / Bailey, J M

Psychological medicine

2014 Volume 45, Issue 7, Page(s) 1379–1388

Abstract: Background: Findings from family and twin studies support a genetic contribution to the development of sexual orientation in men. However, previous studies have yielded conflicting evidence for linkage to chromosome Xq28.: Method: We conducted a ... ...

Abstract	Background: Findings from family and twin studies support a genetic contribution to the development of sexual orientation in men. However, previous studies have yielded conflicting evidence for linkage to chromosome Xq28. Method: We conducted a genome-wide linkage scan on 409 independent pairs of homosexual brothers (908 analyzed individuals in 384 families), by far the largest study of its kind to date. Results: We identified two regions of linkage: the pericentromeric region on chromosome 8 (maximum two-point LOD = 4.08, maximum multipoint LOD = 2.59), which overlaps with the second strongest region from a previous separate linkage scan of 155 brother pairs; and Xq28 (maximum two-point LOD = 2.99, maximum multipoint LOD = 2.76), which was also implicated in prior research. Conclusions: Results, especially in the context of past studies, support the existence of genes on pericentromeric chromosome 8 and chromosome Xq28 influencing development of male sexual orientation.
MeSH term(s)	Adult ; Chromosomes, Human, Pair 8/genetics ; Chromosomes, Human, X/genetics ; Genetic Linkage/genetics ; Genome-Wide Association Study ; Homosexuality, Male/genetics ; Humans ; Male ; Siblings ; United States
Language	English
Publishing date	2014-11-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	217420-0
ISSN	1469-8978 ; 0033-2917
ISSN (online)	1469-8978
ISSN	0033-2917
DOI	10.1017/S0033291714002451
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Zs.B 1003: Show issues

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Article ; Online: A novel Alzheimer disease locus located near the gene encoding tau protein.

Jun, G / Ibrahim-Verbaas, C A / Vronskaya, M / Lambert, J-C / Chung, J / Naj, A C / Kunkle, B W / Wang, L-S / Bis, J C / Bellenguez, C / Harold, D / Lunetta, K L / Destefano, A L / Grenier-Boley, B / Sims, R / Beecham, G W / Smith, A V / Chouraki, V / Hamilton-Nelson, K L /

Ikram, M A / Fievet, N / Denning, N / Martin, E R / Schmidt, H / Kamatani, Y / Dunstan, M L / Valladares, O / Laza, A R / Zelenika, D / Ramirez, A / Foroud, T M / Choi, S-H / Boland, A / Becker, T / Kukull, W A / van der Lee, S J / Pasquier, F / Cruchaga, C / Beekly, D / Fitzpatrick, A L / Hanon, O / Gill, M / Barber, R / Gudnason, V / Campion, D / Love, S / Bennett, D A / Amin, N / Berr, C / Tsolaki, Magda / Buxbaum, J D / Lopez, O L / Deramecourt, V / Fox, N C / Cantwell, L B / Tárraga, L / Dufouil, C / Hardy, J / Crane, P K / Eiriksdottir, G / Hannequin, D / Clarke, R / Evans, D / Mosley, T H / Letenneur, L / Brayne, C / Maier, W / De Jager, P / Emilsson, V / Dartigues, J-F / Hampel, H / Kamboh, M I / de Bruijn, R F A G / Tzourio, C / Pastor, P / Larson, E B / Rotter, J I / O'Donovan, M C / Montine, T J / Nalls, M A / Mead, S / Reiman, E M / Jonsson, P V / Holmes, C / St George-Hyslop, P H / Boada, M / Passmore, P / Wendland, J R / Schmidt, R / Morgan, K / Winslow, A R / Powell, J F / Carasquillo, M / Younkin, S G / Jakobsdóttir, J / Kauwe, J S K / Wilhelmsen, K C / Rujescu, D / Nöthen, M M / Hofman, A / Jones, L / Haines, J L / Psaty, B M / Van Broeckhoven, C / Holmans, P / Launer, L J / Mayeux, R / Lathrop, M / Goate, A M / Escott-Price, V / Seshadri, S / Pericak-Vance, M A / Amouyel, P / Williams, J / van Duijn, C M / Schellenberg, G D / Farrer, L A

Molecular psychiatry

2015 Volume 21, Issue 1, Page(s) 108–117

Abstract: APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ ( ... ...

Abstract	APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.
MeSH term(s)	Alzheimer Disease/genetics ; Apolipoprotein E4/genetics ; Chromosomes, Human, Pair 17 ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide ; tau Proteins/genetics
Chemical Substances	Apolipoprotein E4 ; MAPT protein, human ; tau Proteins
Language	English
Publishing date	2015-03-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/mp.2015.23
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Zs.A 4812: Show issues

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Article ; Online: Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Lambert, J C / Ibrahim-Verbaas, C A / Harold, D / Naj, A C / Sims, R / Bellenguez, C / DeStafano, A L / Bis, J C / Beecham, G W / Grenier-Boley, B / Russo, G / Thorton-Wells, T A / Jones, N / Smith, A V / Chouraki, V / Thomas, C / Ikram, M A / Zelenika, D / Vardarajan, B N /

Kamatani, Y / Lin, C F / Gerrish, A / Schmidt, H / Kunkle, B / Dunstan, M L / Ruiz, A / Bihoreau, M T / Choi, S H / Reitz, C / Pasquier, F / Cruchaga, C / Craig, D / Amin, N / Berr, C / Lopez, O L / De Jager, P L / Deramecourt, V / Johnston, J A / Evans, D / Lovestone, S / Letenneur, L / Morón, F J / Rubinsztein, D C / Eiriksdottir, G / Sleegers, K / Goate, A M / Fiévet, N / Huentelman, M W / Gill, M / Brown, K / Kamboh, M I / Keller, L / Barberger-Gateau, P / McGuiness, B / Larson, E B / Green, R / Myers, A J / Dufouil, C / Todd, S / Wallon, D / Love, S / Rogaeva, E / Gallacher, J / St George-Hyslop, P / Clarimon, J / Lleo, A / Bayer, A / Tsuang, D W / Yu, L / Tsolaki, M / Bossù, P / Spalletta, G / Proitsi, P / Collinge, J / Sorbi, S / Sanchez-Garcia, F / Fox, N C / Hardy, J / Deniz Naranjo, M C / Bosco, P / Clarke, R / Brayne, C / Galimberti, D / Mancuso, M / Matthews, F / Moebus, S / Mecocci, P / Del Zompo, M / Maier, W / Hampel, H / Pilotto, A / Bullido, M / Panza, F / Caffarra, P / Nacmias, B / Gilbert, J R / Mayhaus, M / Lannefelt, L / Hakonarson, H / Pichler, S / Carrasquillo, M M / Ingelsson, M / Beekly, D / Alvarez, V / Zou, F / Valladares, O / Younkin, S G / Coto, E / Hamilton-Nelson, K L / Gu, W / Razquin, C / Pastor, P / Mateo, I / Owen, M J / Faber, K M / Jonsson, P V / Combarros, O / O'Donovan, M C / Cantwell, L B / Soininen, H / Blacker, D / Mead, S / Mosley, T H / Bennett, D A / Harris, T B / Fratiglioni, L / Holmes, C / de Bruijn, R F / Passmore, P / Montine, T J / Bettens, K / Rotter, J I / Brice, A / Morgan, K / Foroud, T M / Kukull, W A / Hannequin, D / Powell, J F / Nalls, M A / Ritchie, K / Lunetta, K L / Kauwe, J S / Boerwinkle, E / Riemenschneider, M / Boada, M / Hiltuenen, M / Martin, E R / Schmidt, R / Rujescu, D / Wang, L S / Dartigues, J F / Mayeux, R / Tzourio, C / Hofman, A / Nöthen, M M / Graff, C / Psaty, B M / Jones, L / Haines, J L / Holmans, P A / Lathrop, M / Pericak-Vance, M A / Launer, L J / Farrer, L A / van Duijn, C M / Van Broeckhoven, C / Moskvina, V / Seshadri, S / Williams, J / Schellenberg, G D / Amouyel, P

Nature genetics

2013 Volume 45, Issue 12, Page(s) 1452–1458

Abstract: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide ... ...

Abstract	Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
MeSH term(s)	Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Case-Control Studies ; Cohort Studies ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study/statistics & numerical data ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2013-10-27
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng.2802
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Article ; Online: Utility of blood pressure genetic risk score in admixed Hispanic samples.

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Article ; Online: The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.

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Article: Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function.

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Article ; Online: Targeted sequencing of ABCA7 identifies splicing, stop-gain and intronic risk variants for Alzheimer disease.

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Article ; Online: Genome-wide scan demonstrates significant linkage for male sexual orientation.

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Article ; Online: A novel Alzheimer disease locus located near the gene encoding tau protein.

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Article ; Online: Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

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