Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide association study of ischemic stroke subtypes.

Stroke
Authors
Keywords
Abstract

BACKGROUND AND PURPOSE: Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke.

METHODS: The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14,549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research-generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived.

CONCLUSIONS: The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.

Year of Publication
2013
Journal
Stroke
Volume
44
Issue
10
Pages
2694-702
Date Published
2013 Oct
ISSN
1524-4628
URL
DOI
10.1161/STROKEAHA.113.001857
PubMed ID
24021684
PubMed Central ID
PMC4056331
Links
Grant list
N01WH42124 / WH / WHI NIH HHS / United States
HL34594 / HL / NHLBI NIH HHS / United States
Z01 AG000954-06 / AG / NIA NIH HHS / United States
N01WH32102 / WH / WHI NIH HHS / United States
U01 HG 004446 / HG / NHGRI NIH HHS / United States
Z01 AG000015 / AG / NIA NIH HHS / United States
R01 NS042618 / NS / NINDS NIH HHS / United States
R01 NS45012 / NS / NINDS NIH HHS / United States
R01 NS045012 / NS / NINDS NIH HHS / United States
R01 NS042733 / NS / NINDS NIH HHS / United States
N01WH42112 / WH / WHI NIH HHS / United States
N01WH42119 / WH / WHI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
095626 / Wellcome Trust / United Kingdom
N01WH32122, / WH / WHI NIH HHS / United States
N01WH32112 / WH / WHI NIH HHS / United States
N01WH32101 / WH / WHI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
R01 NS030678 / NS / NINDS NIH HHS / United States
N01WH32119 / WH / WHI NIH HHS / United States
N01WH32105 / WH / WHI NIH HHS / United States
N01WH42132 / WH / WHI NIH HHS / United States
N01WH42121 / WH / WHI NIH HHS / United States
N01WH42113 / WH / WHI NIH HHS / United States
N01WH42125 / WH / WHI NIH HHS / United States
Medical Research Council / United Kingdom
CA87969 / CA / NCI NIH HHS / United States
HL088521 / HL / NHLBI NIH HHS / United States
K23 NS042695 / NS / NINDS NIH HHS / United States
R01 NS073346 / NS / NINDS NIH HHS / United States
Department of Health / United Kingdom
N01WH32106 / WH / WHI NIH HHS / United States
N01WH42129 / WH / WHI NIH HHS / United States
P50 NS055977 / NS / NINDS NIH HHS / United States
N01WH42108 / WH / WHI NIH HHS / United States
CA49449 / CA / NCI NIH HHS / United States
N01WH42118 / WH / WHI NIH HHS / United States
K23 NS042720 / NS / NINDS NIH HHS / United States
R01NS042618 / NS / NINDS NIH HHS / United States
N01WH32113 / WH / WHI NIH HHS / United States
R37 NS029993 / NS / NINDS NIH HHS / United States
R01 NS27517 / NS / NINDS NIH HHS / United States
N01WH42120 / WH / WHI NIH HHS / United States
N01WH32118 / WH / WHI NIH HHS / United States
N01WH42131 / WH / WHI NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
Intramural NIH HHS / United States
N01WH42109 / WH / WHI NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
Z01 AG000015-50 / AG / NIA NIH HHS / United States
N01WH42114 / WH / WHI NIH HHS / United States
U01 NS069208 / NS / NINDS NIH HHS / United States
R01 NS039987 / NS / NINDS NIH HHS / United States
R01 NS059727 / NS / NINDS NIH HHS / United States
N01WH42107 / WH / WHI NIH HHS / United States
U01 NS041588 / NS / NINDS NIH HHS / United States
N01WH32111 / WH / WHI NIH HHS / United States
R01 HL034594 / HL / NHLBI NIH HHS / United States
N01WH42130 / WH / WHI NIH HHS / United States
N01WH42117 / WH / WHI NIH HHS / United States
WT084724MA / Wellcome Trust / United Kingdom
N01WH42115 / WH / WHI NIH HHS / United States
085475/B/08/Z / Wellcome Trust / United Kingdom
UL1 TR000448 / TR / NCATS NIH HHS / United States
K23NS042695 / NS / NINDS NIH HHS / United States
U01NS38529-04A1 / NS / NINDS NIH HHS / United States
N01WH42111 / WH / WHI NIH HHS / United States
U01 HG004436 / HG / NHGRI NIH HHS / United States
R01NS059727 / NS / NINDS NIH HHS / United States
N01WH32109 / WH / WHI NIH HHS / United States
N01WH32108 / WH / WHI NIH HHS / United States
U01 NS038529 / NS / NINDS NIH HHS / United States
Chief Scientist Office / United Kingdom
U01 NS069208-01 / NS / NINDS NIH HHS / United States
UL1 TR000077 / TR / NCATS NIH HHS / United States
N01WH42122 / WH / WHI NIH HHS / United States
R01 HL088521 / HL / NHLBI NIH HHS / United States
R01 CA049449 / CA / NCI NIH HHS / United States
HHSN268200782096C / PHS HHS / United States
N01WH32100 / WH / WHI NIH HHS / United States
U01 CA049449 / CA / NCI NIH HHS / United States
N01WH42123 / WH / WHI NIH HHS / United States
NS 030678 / NS / NINDS NIH HHS / United States
N01WH32115 / WH / WHI NIH HHS / United States
N01WH44221 / WH / WHI NIH HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
R01 NS39987 / NS / NINDS NIH HHS / United States
U54 RR020278 / RR / NCRR NIH HHS / United States
085475/Z/08/Z / Wellcome Trust / United Kingdom
Z01 AG000954 / AG / NIA NIH HHS / United States
R01 NS42733 / NS / NINDS NIH HHS / United States
N01WH24152 / WH / WHI NIH HHS / United States
N01WH42110 / WH / WHI NIH HHS / United States
N01WH42126 / WH / WHI NIH HHS / United States
N01WH42116 / WH / WHI NIH HHS / United States