한빛사논문
- 조회311
Sanghun Lee1,2,3, Julian Hecker2, Georg Hahn3, Kristina Mullin4, Alzheimer’s Disease Neuroimaging Initiative(ADNI)#, Sharon M. Lutz3,5, Rudolph E. Tanzi4, Christoph Lange2,3, Dmitry Prokopenko4
1Department of Medical Consilience, Division of Medicine, Graduate school, Dankook University, Yongin-si, Gyeonggi-do, South Korea
2Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
3Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
4Genetics and Aging Unit and McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
5Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Healthcare Institute, Boston, Massachusetts, USA
CORRESPONDING AUTHORS : Rudolph E. Tanzi, Christoph Lange, Dmitry Prokopenko
Abstract
Introduction: Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry.
Methods: We utilized the whole genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) including 35,569 participants. A total of 25,459 subjects in four distinct populations (African ancestry, non-Hispanic White, admixed Hispanic, and Asian) were analyzed.
Results: We found that nine DSLs showed significant heterogeneity across populations. Single nucleotide polymorphism (SNP) rs2075650 in translocase of outer mitochondrial membrane 40 (TOMM40) showed the largest heterogeneity (Cochran's Q = 0.00, I2 = 90.08), followed by other SNPs in apolipoprotein C1 (APOC1) and apolipoprotein E (APOE). Two additional loci, signal-induced proliferation-associated 1 like 2 (SIPA1L2) and solute carrier 24 member 4 (SLC24A4), showed significant heterogeneity across populations.
Discussion: We observed substantial heterogeneity for the APOE-harboring 19q13.32 region with TOMM40/APOE/APOC1 genes. The largest risk effect was seen among African Americans, while Asians showed a surprisingly small risk effect.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-04)
- 국내+국외 연구진
- 의약학 > 유전 및 유전체의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
