Table 14.

Genetic predisposition and risk of AF—population-based studies

Study	Design	Subjects	FU	Familial AF history	AF, %	Risk* (95% Cl)
Fox et al236  Framngham  Heart Study	Prospective cohort Population-based epidemiological study	2243 O 1165 women 1078 men At least 30 yrs	16 yrs	681—at least 1 parent had documented AF	n = 70	Parental AF vs. no FH OR 1.85 (1.12–3.06; P = 0.02) Parental AF vs. no FH <75 years (O and P) OR 323 (1.87–5.58; P< 0.001) Parental AF vs. no FH <75 years (O w/o overt clinical heart disease) OR 3.17 (1.71 –5.86; P< 0.001)
Amar et al237  Iceland cohort	Populad on-based cohort	5269 pts with AF	–	AF risk in first to fifth degree relatives	–	First degree relative RR 1.77 (1.67 = 1.88 P = 0.001) First degree relative <60 years old RR 4.67 (3.57–6.08, P = 0.001)
Gundlund et al238  Denmark cohort	Populad on-based study	New-onset AF 67 310 mothers—64 yrs 103 822 fathers—70 yrs 11 800 siblings—46 yrs		AF screening: 133516 maternal O 221 774 paternal O 21 448 sibling O	2536 (1.9%) 2906 (1.3%) 292 (1.4%)	RR compared with general Denmark population 3.37 (3.21–3.53) 181 (2.69–193) 5.20 (4.61–5.85)
Zolleretd.235  Sweden cohort	Populad on-based case-controlled study	300 586 individuals with AF/AFl multiplex families		1 parent ≤49 yrs 2 parents ≤49 yrs ≥1 sibling ≤49 yrs ≥2 siblings ≤49 yrs	Case vs. control 22.6 vs. 13.6% 22.8 vs. 11.9% 2.0 vs. 0.2% 2.1 vs. 0.5% 14.7 vs. 5.6% 8.1 vs. 13% 19 vs. 0.6% 1.4 vs. 0.2%	OR 1.95 (1.89–100) OR 133 (123–144) OR 3.6 (3.3–3.92) OR 5.04 (4.36–5.28) OR 3.08 (3.0–3.16) OR 4.06 (3.79 –4.41) OR 5.72 (5.28–6.19) OR 8.51 (6.49–11.15)
Lubitz et al240  Framingham Heart Study	Prospective cohort	4421 participants	–	Familial AF—1185 Premature familial AF (<65 yrs) −351	Overall 440 Familial AF vs. no FH 5.8 vs. 3.1%	Presence of any first degree familial AF vs. no HR 1.4 (1.13–1.74, P = 0.002) Presence of premature familial AF (<65 years) HR 2.01 (1.49–171, P < 0.001) Number of first degree relative with AF—risk per each additional affected member HR 1.24 (1.05–1.46, P=0.01)
Oyen et al241  Denmark cohort	Prospective cohort	3 985 446 individuals Lone AF—9507 subjects <60 yrs	31 yrs	First degree relative Second degree relative Number of affected first degree relatives 1 affected ≥2 affected Age at onset of lone AF for cohort member and first degree relative <30 yrs for both <40 yrs for both	n = 269 n= 19 n = 264 n = 5 N/A n = 31	IRR 3.48 (3.08–3.93) IRR 1.64 (1.04–159) IRR 3.45 (3.05–3.9) IRR 6.24 (159–15.0) IRR 8.53 (3.82–19.0) IRR 5.42 (3.8–7.72)

AF, atrial fibrillation; Cl, confidence interval; FH, family history; FU, follow-up; HR, hazard ratio; IRR, incidence rate ratio; O, offspring; OR, odds ratio; P, parent; pts, patients; RR, relative risk; yrs, years.