Relative risk for Alzheimer disease based on complete family history

Lisa A Cannon-Albright, Norman L Foster, Karen Schliep, James M Farnham, Craig C Teerlink, Heydon Kaddas, Joann Tschanz, Chris Corcoran, John S K Kauwe, Lisa A Cannon-Albright, Norman L Foster, Karen Schliep, James M Farnham, Craig C Teerlink, Heydon Kaddas, Joann Tschanz, Chris Corcoran, John S K Kauwe

Abstract

Objective: The inherited component for Alzheimer disease (AD) risk has focused on close relatives; consideration of the full family history may improve accuracy and utility of risk estimates.

Methods: A population resource including a genealogy of Utah pioneers from the 1800s linked to Utah death certificates was used to estimate relative risk for AD based on specific family history constellations, including from first- to third-degree relatives.

Results: Any affected first-degree relatives (FDR) significantly increased risk of AD (≥1 FDRs: relative risk [RR] 1.73, 95% confidence interval [CI] [1.59-1.87]; ≥2 FDRs: RR 3.98 [3.26-4.82]; ≥3 FDRs: RR 2.48 [1.07-4.89]; ≥4 FDRs: RR 14.77 [5.42-32.15]). Affected second-degree relatives (SDR) increased risk even in the presence of affected FDRs (FDR = 1 with SDR = 2: RR 21.29 [5.80-54.52]). AD only in third-degree relatives (TDR) also increased risk (FDR = 0, SDR = 0, TDR ≥3: RR 1.43 [1.21-1.68]). Mixed evidence was observed for differences in risk based on maternal compared to paternal inheritance; higher risks for men than women with equivalent family history, and higher risk for individuals with at least one affected FDR regardless of the relative's age at death, were observed.

Conclusions: This population-based estimation of RRs for AD based on family history ascertained from extended genealogy data indicates that inherited genetic factors have a broad influence, extending beyond immediate relatives. Providers should consider the full constellation of family history when counseling patients and families about their risk of AD.

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

References

    1. Herbert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology 2013;80:1778–1783.
    1. Karch CM, Goate AM. Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry 2015;77:43–51.
    1. Guerreiro RJ, Gustafson DR, Hardy J. The genetic architecture of Alzheimer's disease: beyond APP, PSENs and APOE. Neurobiol Aging 2012;33:437–456.
    1. Karch CM, Cruchaga C, Goate AM. Alzheimer's disease genetics: from the bench to the clinic. Neuron 2014;83:11–26.
    1. Ward A, Crean S, Mercaldi CJ, et al. . Prevalence of apolipoprotein e4 genotype and homozygotes (APOE er/r) among patients diagnosed with Alzheimer’s disease: a systemic review and meta-analysis. Neuroepidemiology 2012;38:1–17.
    1. Loy CT, Schofield PR, Turner AM, Kwok JB. Genetics of dementia. Lancet 2014;383:828–840.
    1. Holtzman DM, Herz J, Bu G. Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med 2012;2:a006312.
    1. Lambert JC, Ibrahim-Verbaas CA, Harold D, et al. . Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet 2013;45:1452–1458.
    1. Jonsson T, Stefansson H, Steinberg S, et al. . Variant of TREM2 associated with the risk of Alzheimer's disease. N Engl J Med 2013;368:107–116.
    1. Guerreiro R, Wojtas A, Bras J, et al. . TREM2 variants in Alzheimer's disease. N Engl J Med 2013;368:117–127.
    1. Scheltens P, Blennow K, Breteler MM, et al. . Alzheimer's disease. Lancet 2016;388:505–517.
    1. Ridge PG, Hoyt KB, Boehme K, et al. . Assessment of the genetic variance of late-onset Alzheimer's disease. Neurobiol Aging 2016;41:200-e20.
    1. Kauppi K, Fan CC, McEvoy LK, et al. . Combining polygenic hazard score with volumetric MRI and cognitive measures improves prediction of progression from mild cognitive impairment to Alzheimer's disease. Front Neurosci 2018;12:260.
    1. Tan CH, Fan CC, Mormino EC, et al. . Polygenic hazard score: an enrichment marker for Alzheimer's associated amyloid and tau deposition. Acta Neuropathol 2018;135:85–93.
    1. Chaudhury S, Patel T, Barber IS, et al. . Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease. Neurobiol Aging 2018;62:244.e1–244.e8.
    1. Cruchaga C, Del-Aguila JL, Saef B, et al. . Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms. Alzheimers Dement 2018;14:205–214.
    1. Desikan RS, Fan CC, Wang Y, et al. . Genetic assessment of age-associated Alzheimer disease risk: development and validation of a polygenic hazard score. PLoS Med 2017;14:e1002258.
    1. Escott-Price V, Shoai M, Pither R, Williams J, Hardy J. Polygenic score prediction captures nearly all common genetic risk for Alzheimer's disease. Neurobiol Aging 2017;49:214.e7–214.e11.
    1. Donix M, Small GW, Bookheimer SY. Family history and APOE-4 genetic risk in Alzheimer's disease. Neuropsychol Rev 2012;22:298–309.
    1. Cupples LA, Farrer LA, Sadovnick AD, Relkin N, Whitehouse P, Green RC. Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: the REVEAL study. Genet Med 2004;6:192–196.
    1. Fratiglioni L, Ahlbom A, Viitanen M, Winblad B. Risk factors for late-onset Alzheimer's disease: a population-based, case-control study. Ann Neurol 1993;33:258–266.
    1. van Duijn CM, Clayton D, Chandra V, et al. . Familial aggregation of Alzheimer’s disease and related disorders: a collaborative re-analysis of case control studies. Int J Epidemiol 1991;20:S13–S20.
    1. Cannon Albright LA. Utah family-based analysis: past, present and future. Hum Hered 2008;65:209–220.
    1. Kauwe JS, Ridge PG, Foster NL, Cannon-Albright LA. Strong evidence for a genetic contribution to late-onset Alzheimer's disease mortality: a population-based study. PLoS One 2013;8:e77087.
    1. Agresti A. Categorical Data Analysis. New York: Wiley; 1990.
    1. Farrer LA, O'Sullivan DM, Cupples LA, Growdon JH, Myers RH. Assessment of genetic risk for Alzheimer's disease among first-degree relatives. Ann Neurol 1989;25:485–493.
    1. Liddell MB, Lovestone S, Owen MJ. Genetic risk of Alzheimer's disease: advising relatives. Br J Psychiatry 2001;178:7–11.
    1. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. Nat Rev Neurol 2011;7:137–152.
    1. Van Cauwenberghe C, Van Broeckhoven C, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med 2016;18:421–430.
    1. Green RC, Cupples LA, Go R, et al. . Risk of dementia among white and African American relatives of patients with Alzheimer disease. JAMA 2002;287:329–336.
    1. Cannon-Albright LA, Dintelman S, Maness T, et al. . A population genealogy resource shows evidence of familial clustering for Alzheimer’s disease. Neurol Genet 2018;4:e249.
    1. Li G, Silverman JM, Smith CJ, et al. . Age at onset and familial risk in Alzheimer's disease. Am J Psychiatry 1995;152:424–430.
    1. Lautenschlager NT, Cupples LA, Rao VS, et al. . Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: what is in store for the oldest old? Neurology 1996;46:641–650.
    1. Farrer LA, Cupples LA, van Duijn CM, et al. . Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives. Ann Neurol 1995;38:797–808.
    1. van Duijn CM, Farrer LA, Cupples LA, Hofman A. Genetic transmission of Alzheimer's disease among families in a Dutch population based study. J Med Genet 1993;30:640–646.
    1. Mosconi L, Berti V, Swerdlow RH, Pupi A, Duara R, de Leon M. Maternal transmission of Alzheimer’s disease: prodromal metabolic phenotype and the search for genes. Hum Genomics 2010;4:170–193.
    1. Ridge PG, Maxwell TJ, Corcoran CD, et al. . Mitochondrial genomic analysis of late onset Alzheimer’s disease reveals protective haplogroups H6A1A/H6A1B: the Cache County Study on Memory in Aging. PLoS One 2012;7:e45134.
    1. Edland SD, Silverman JM, Peskind ER, Tsuang D, Wijsman E, Morris JC. Increased risk of dementia in mothers of AD cases: evidence for maternal inheritance. Neurology 1996;47:254–256.
    1. de Bruijn RF, Ikram MA. Cardiovascular risk factors and future risk of Alzheimer's disease. BMC Med 2014;12:130.
    1. de Bruijn RF, Bos MJ, Portegies ML, et al. . The potential for prevention of dementia across two decades: the prospective, population-based Rotterdam Study. BMC Med 2015;13:132.
    1. Ngandu T, Lehtisalo J, Solomon A, et al. . A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 2015;385:2255–2263.
    1. Rosenberg A, Ngandu T, Rusanen M, et al. . Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: the FINGER trial. Alzheimer Dement 2018;14:263–270.
    1. Allan CL, Behrman S, Ebmeier KP. Early diagnosis beneficial in Alzheimer's disease. Practitioner 2013;257:15–22.
    1. Taylor DP, Burt RW, Williams MS, Haug PJ, Cannon-Albright LA. Population-based family history-specific risks for colorectal cancer: a constellation approach. Gastroenterology 2010;138:877–885.
    1. Albright FS, Stephenson RA, Agarwal N, et al. . Prostate cancer risk prediction based on complete prostate cancer family history. Prostate 2015;75:390–398.
    1. Frecker MF, Pryse-Phillips WE, Strong HR. Alzheimer's disease death certificates. Neurology 1995;45:2298–2299.
    1. Raiford K, Anton-Johnson S, Haycox Z, et al. . CERAD part VII: accuracy of reporting dementia on death certificates of patients with Alzheimer's disease. Neurology 1994;44:2208–2209.
    1. Ostbye T, Taylor DH, Jr., Clipp EC, Scoyoc LV, Plassman BL. Identification of dementia: agreement among national survey data, Medicare claims, and death certificates. Health Serv Res 2008;43:313–326.
    1. Tschanz JT, Corcoran C, Skoog I, et al. . Dementia: the leading predictor of death in a defined elderly population: the Cache County Study. Neurology 2004;62:1156–1162.
    1. Gill TM, Gahbauer EA, Han L, Allore HG. Trajectories of disability in the last year of life. N Engl J Med 2010;362:1173–1180.
    1. Martyn CN, Pippard EC. Usefulness of mortality data in determining the geography and time trends of dementia. J Epidemiol Community Health 1988;42:134–137.
    1. McLellan T, Jorde LB, Skolnick MH. Genetic distances between the UT Mormons and related populations. Am J Hum Genet 1984;36:836–857.
    1. Jorde LB. Inbreeding in the Utah Mormons: an evaluation of estimates based on pedigrees, isonymy, and migration matrices. Ann Hum Genet 1989;53:339–355.

Source: PubMed

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